Steric effect in the formation of hydrogen bonded complexes of isopropylamine with alicyclic ethers by ultrasonic and DFT approach

https://doi.org/10.1016/j.molliq.2020.113910Get rights and content

Highlights

  • H-bonded interaction of isopropylamine with two alicyclic ethers was identified.

  • Stability of complexes was analysed through ultrasonic and DFT methods.

  • DFT study shows the interaction is through inter molecular hydrogen bond.

  • Formation constant and interaction energy values revealed presence of weak interaction.

  • Comparison of results in NPA and IPA interactions with ethers showed the steric effect.

Abstract

Experimental (acoustical) and theoretical (DFT) analyses have been undertaken to unravel the possibility of hydrogen bonded complexes of isopropylamine (IPA) with two industrially important cyclic ethers, tetrahydrofuran (THF) and 1,4 dioxane (DIOX) in n – hexane at 303.15 K and at atmospheric pressure. The trend in acoustical and excess parameters with concentration revealed the dominance of structure breaking behavior of like molecules of solute components and formation of intermolecular H-bonding between IPA and ethers in the two ternary systems at room temperature. The data obtained through DFT studies further support the existence of intermolecular H-bond between amine and ethers. The strength of interactions has been assessed from the formation constants (K) determined by acoustic method and interaction energies by DFT respectively. The reduced density gradient (RDG) and non-covalent interaction (NCI) plots clearly exhibit the presence of intermolecular interactions in the two systems. The stability of these complexes and the strength of the interactions are explained with the structure of ether. Comparison of K and interaction energy values in the present study with those obtained in n-propylamine interactions with ethers showed steric effect in the formation of complex of IPA with the two ethers.

Introduction

Organic solvents are widely used at any step of the synthetic route of an active drug intermediate or excipients. They are also employed in pharmaceutical formulation process. Major role of solvent in the synthesis of drug is homogenization of reactants within the reaction medium and also to enhance the rate of the reaction as well as the yield of the product [1]. The choice of solvents in the manufacture of drugs is critical for various reasons. Toxicity, mutagenicity and environmental impact of solvents are to be considered in the choice of solvent in pharmaceutical industry. Aqueous, non-aqueous or mixed solvents are generally employed in the drug industry depending on the requirements of the synthesis. The alicyclic ethers have been found to be potential solvents in pharmaceutical industry [2,3]. Catalyst free one pot protocol sonication method has been developed for the synthesis of biologically important rhodanine derivatives in aqueous and non-aqueous media like THF [4]. THF is also employed as effective solvent in the preparation of an intermediate compound in the manufacture of the antimalarial drug hydroxychloroquine [5]. 1,4-Dioxane is a six membered heterocyclic ether widely used in the preparation of polymers which exists in different conformers and the proportions of its conformers in the liquid phase is not yet established [[6], [7], [8], [9], [10], [11], [12], [13]]. The nature and strength of molecular interactions depends on varied structures of components in the solutions which can be identified by the non- ideal behavior of multicomponent liquid systems [14,15]. The intermolecular interactions drastically modify the physical properties of solutions. Further, the study of molecular complexes of amines and ethers is significant due to their biological importance [16,17]. There are several reports on the molecular interaction between components of primary, secondary, tertiary and cyclic amines with aromatic hydrocarbon, non-electrolyte solvents and cyclic ethers [[18], [19], [20], [21], [22], [23], [24], [25]]. However, there is only scanty data on isopropyl amine – alicyclic ether binary systems and there is a need for further investigation. Ultrasonic studies of hydrogen bonded complexes of anisole with aromatic primary and secondary amines in n-hexane solvent were investigated and theoretical studies were also applied to confirm the conclusions drawn from ultrasonic studies of molecular interactions [[26], [27], [28]]. Hydrogen bond plays vital role in determining the structures and functions of molecular complexes through various H-bonding pattern in molecular assemblies in solutions, solid state as well as in liquid crystalline (LC) state. The importance of H-bonding in liquid crystalline systems was well established and this property in supra-molecular assembly has been used as a tool for design of new LC materials [[29], [30], [31]].

In our earlier papers we reported investigation on the molecular interactions of alicyclic ethers with benzyl amine and n-propyl amine [28,32]. The most favoured amine donor used in transaminase catalyzed enzyme reactions is IPA since it is cheap and achiral [33]. It is also widely used in the synthesis and formulation of insecticides and herbicides [34,35]. The present work is aimed at unraveling the molecular interactions of the two alicyclic ethers [THF and DIOX] with iso-propylamine in n – hexane medium by ultrasonic and DFT studies. Molecular electrostatic potential (MEP) is very useful tool in analyzing the strength of interactions [[36], [37], [38], [39]]. The present study considers computational (MEP contour) as well as experimental techniques to characterize the molecular level interactions in ternary systems of IPA with two alicyclic ethers (THF, DIOX) in n-hexane medium. In recent years, the reduced density gradient (RDG) has been found to be a more useful tool to analyze non-covalent interactions. Both strong and weak non-covalent interactions can be identified through RDG, although applications of RDG to stronger interactions are limited [40]. Plots of reduced density gradient (RDG) versus the electron density multiplied by the sign of the second Hessian eigenvalue (λ2) for the two investigated systems were obtained by reported method [41]. The presence of different types of interactions in the two ternary systems is also established from non-covalent interaction (NCI) plots and reduced density gradient (RDG) plots.

Section snippets

Ultrasonic study

The source of organic compounds used in the work, purity, further purification, their boiling points and purity check method are summarized in Table 1. All measurements were made for freshly prepared solutions by mixing accurate masses of pure liquids in the solvent (n-hexane) to obtain the required range of concentrations from 0.02 M to 0.2 M. The measuring instrument was standardized using triple distilled water and the measurement was in good agreement with reported values in the literature.

Ultrasonic study

The measured values of ultrasonic velocity, density and dynamic viscosity are listed in Table 3 for the two ternary systems at 303.15 K. The computed thermo-acoustical properties of the two systems are presented in Table 4 while Table 5 contains the excess properties. The plots of ultrasonic velocity (u), adiabatic compressibility (κ) and internal pressure (πi) as a function of concentration are shown in Fig. 1(a)–(c). The changes in excess velocity (uE), excess free length (LfE) and excess

Conclusion

The trend for the thermo-acoustical properties and excess properties with concentration of the two ternary systems IPA-THF and IPA-DIOX in n-hexane at room temperature establishes the formation of H-bonded complexes between IPA and the two cyclic ethers. Stability constants (K) determined by ultrasonic method and interaction energies computed by DFT procedure showed that IPA-DIOX complex is more stable than IPA-THF complex. Optimized geometries of the two complexes in n-hexane contained N-H…O

Declaration of competing interest

There is no conflict of interest in publishing the manuscript in the Journal of Molecular liquids. The authors also informed that this manuscript is not funded by any agency.

Acknowledgements

The authors thank the Management of The New College, for the facilities provided and the encouragements shown towards this work. The authors also thank the e – learning centre of The New College, funded by DST e FIST (C.Dy.No.2644/IFD/2015-2016 dt. 21.08.2015).

References (71)

  • A. Martínez-Felipe et al.

    The role of hydrogen bonding in the phase behaviour of supramolecular liquid crystal dimers

    J. Mol. Struc.

    (2015)
  • S.L. Oswal et al.

    Densities, speeds of sound, isentropic compressibilities, refractive indexes, and viscosities of tetrahydrofuran with haloalkane or alkyl ethanoate at T = 303.15 K

    Thermochim. Acta

    (2005)
  • Manisha Gupta et al.

    Ultrasonic velocity, viscosity and excess properties of binary mixture of tetrahydrofuran with 1-propanol and 2-propanol

    Fluid Phase Equilib.

    (2006)
  • R. Kumar et al.

    Acoustical and spectroscopic investigation of charge transfer complexes of certain aromatic compounds with iodine in n-hexane at 303 K

    J. Mol. Liq.

    (2014)
  • R. Kumar et al.

    Spectroscopic and ultrasonic studies on the hydrogen bonded complexes of aromatic aldehydes with phenol in hexane medium

    J. Mol. Liq.

    (2013)
  • R. Kumar et al.

    Thermo acoustic and spectral investigations of charge transfer interaction between aromatic amine and ketones

    Fluid Phase Equlib

    (2011)
  • W. Humphrey et al.

    VMD - visual molecular dynamics

    J. Molec. Graphics

    (1996)
  • E. Espinosa et al.

    Hydrogen bond strengths revealed by topological analyses of experimentally observed electron densities

    Chem. Phys. Lett.

    (1998)
  • Katarzyna Grodowska et al.

    Organic solvents in the pharmaceutical industry

    Acta Pol. Pharm. Drug Res.

    (2010)
  • Daniel Carriazo et al.

    Deep-eutectic solvents playing multiple roles in the synthesis of polymers and related materials

    Chem. Soc. Rev.

    (2012)
  • C.P. Li et al.

    Role of solvents in coordination supramolecular systems

    Chem. Commun.

    (2011)
  • Micheline Draye et al.

    Ultrasound for drug synthesis: a green approach

    Pharmaceuticals

    (2020)
  • Eric Yu et al.

    High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

    Beilstein J. Org. Chem.

    (2018)
  • W. Liu et al.

    Effect of aggregation of p-phenylphenol on enzymatic polymer synthesis in dioxane/water mixture

    J. Polym. Sci. A Polym. Chem.

    (1995)
  • A. Joseph Akkara et al.

    Synthesis and characterization of polymers produced by horseradish peroxidase in dioxane

    J. Poly. Sci., Part A

    (1991)
  • Guillaume Gody et al.

    Rapid and quantitative one-pot synthesis of sequence-controlled polymers by radical polymerization

    Nat. Commun.

    (2013)
  • Darren M. Chapman et al.

    Ab initio conformational analysis of 1,4-dioxane

    J. Phys. Chem. A

    (1997)
  • S.S. Shastri et al.

    Surface tension of some binary organic solutions of alkyl benzenes and 1-alkanols

    J. Chem. Eng. Data

    (1993)
  • A. Aucejo et al.

    Densities, viscosities and refractive indices of some n-alkane binary liquid systems at 298.15 K

    J. Chem. Eng. Data

    (1995)
  • Hans-Jürgen Buschmann et al.

    Complexation of some amine compounds by macrocyclic receptors

    J. of Inclusion Phenomena and Macrocyclic Chemistry

    (2001)
  • George W. Gokel et al.

    Crown ethers: sensors for ions and molecular scaffolds for materials and biological models

    Chem. Rev.

    (2004)
  • Amalendu Pal et al.

    Mixing properties for binary liquid mixtures of methyl tert-butyl ether with propylamine and dipropylamine at temperatures from (288.15 to 308.15) K

    J. Chem. Eng. Data

    (2010)
  • Zubin R. Master et al.

    Molecular interaction study through experimental and theoretical volumetric, transport and refractive properties of N-ethylaniline with aryl and alkyl ethers at several temperatures

    Phys. and Chem. of Liq.

    (2016)
  • V. Pandiyan et al.

    Thermodynamic and acoustic properties of binary mixtures of ethers. 2.diisopropyl ether with arylamines at (303.15, 313.15 and 323.15) k and application of ERAS model to aniline mixtures with diisopropyl ether and oxolane

    J. Chem. Eng. Data

    (2011)
  • Cited by (6)

    • Study of the crystal structure, H-bonding and noncovalent interactions of novel cocrystal by systematic computational search approach

      2022, Journal of Molecular Structure
      Citation Excerpt :

      The ε is an indicator of the localization and delocalization of the electron cloud around the corresponding atoms at BCPs, thus indicating the instability of each interaction. The smaller value of the ε corresponds to the delocalization of the electrons at that particular bond, and the higher value corresponds to the localisation of the electrons [42]. The C1-H1…O5 is found to be having the least ε value.

    • A novel method for selective recovery of indium from end-of-life liquid crystal displays by 15-crown-5 ether and its derivatives

      2021, Hydrometallurgy
      Citation Excerpt :

      The calculated results and the three-dimensional HOMO and LUMO plots of the complexes are shown in Fig. 7. A high HOMO-LUMO gap generally restricts electron mobility, representing the high stability of a chemical species (Hussain et al., 2020). It is seen that the HOMO-LUMO gap values of 15C5, B15C5 and TB15C5 are generally larger than that of the corresponding complexes with In3+, indicating the decrease in stability after the complexation of the crown ethers with In3+.

    • The non-covalent interaction studies of o-nitrophenol and methyl acetate in benzene: By ultrasonics, FTIR and DFT methods

      2021, Materials Today: Proceedings
      Citation Excerpt :

      Recently, the non-covalent interactions are a more valuable method for the analysis of the Reduced Density Gradient (RDG). The RDG can differentiate strong and weak NCI’s; however, the relevance of RDG to stronger interactions are narrowed [40–41]. The NCI plots for the complex are shown in the Figs. 6-7, from the NCI plots by (N-O….

    View full text