A Theoretical Study of the Preferred
Reaction Mechanism Between
Chloroacetic Acid and Thiourea
Mwadham M. Kabanda and Kgalaletso P. Otukile
Abstract 2-iminothiazolidin-4-one derivatives are known to possess various biological activities such as anticancer, antiviral, antibacterial and antifungal, making
them interesting lead compounds in the design of pharmaceutically useful drugs. For
instance, recent studies have shown that 2-imino-thiazolidin-4-one derivatives are
vital scaffold for the design of potent, orally active lysophospholipid receptor agonists selected for clinical development. Despite their potential application in drug
development, the reaction mechanism for the formation of 2-iminothiazolidin-4-one
is still a challenge. The current theoretical work attempts to study the mechanistic
pathways for the formation of 2-iminothiazolidin-4-one from chloroacetic acid and
thiourea. Calculations were performed with MP2 and DFT methods (with M06-2X
and M11-L functionals) using the 6-31+G(d,p) and the 6-311++G(3df,2p) basis sets.
The study was performed in vacuo and in water solution. The influence of water was
assessed by predicting its role as bulk solvent. The results of the study show that the
reaction between chloroacetic acid and thiourea may involve the iminothiol form of
thiourea rather than the thione form. The reaction is spontaneous and prefers to occur
in vacuo to occurring in water solution.
Keywords DFT calculations · Nucleophilic substitution · Tautomerism ·
Hydrogen bonding
M. M. Kabanda (B) · K. P. Otukile
Department of Chemistry, Faculty of Natural and Agricultural Sciences, North-West University,
Private Bag X2046, Mmabatho 2735, South Africa
e-mail: mwadham.kabanda@nwu.ac.za
Material Science Innovation and Modelling (MaSIM) Research Focus Area,
Faculty of Natural and Agricultural Sciences, North-West University,
Private Bag X 2046, Mmabatho 2735, South Africa
© Springer Nature Switzerland AG 2020
L. Mammino et al. (eds.), Advances in Quantum Systems in Chemistry,
Physics, and Biology, Progress in Theoretical Chemistry and Physics 32,
https://doi.org/10.1007/978-3-030-34941-7_7
119
Reaction Mechanism Between
Chloroacetic Acid and Thiourea
Mwadham M. Kabanda and Kgalaletso P. Otukile
Abstract 2-iminothiazolidin-4-one derivatives are known to possess various biological activities such as anticancer, antiviral, antibacterial and antifungal, making
them interesting lead compounds in the design of pharmaceutically useful drugs. For
instance, recent studies have shown that 2-imino-thiazolidin-4-one derivatives are
vital scaffold for the design of potent, orally active lysophospholipid receptor agonists selected for clinical development. Despite their potential application in drug
development, the reaction mechanism for the formation of 2-iminothiazolidin-4-one
is still a challenge. The current theoretical work attempts to study the mechanistic
pathways for the formation of 2-iminothiazolidin-4-one from chloroacetic acid and
thiourea. Calculations were performed with MP2 and DFT methods (with M06-2X
and M11-L functionals) using the 6-31+G(d,p) and the 6-311++G(3df,2p) basis sets.
The study was performed in vacuo and in water solution. The influence of water was
assessed by predicting its role as bulk solvent. The results of the study show that the
reaction between chloroacetic acid and thiourea may involve the iminothiol form of
thiourea rather than the thione form. The reaction is spontaneous and prefers to occur
in vacuo to occurring in water solution.
Keywords DFT calculations · Nucleophilic substitution · Tautomerism ·
Hydrogen bonding
M. M. Kabanda (B) · K. P. Otukile
Department of Chemistry, Faculty of Natural and Agricultural Sciences, North-West University,
Private Bag X2046, Mmabatho 2735, South Africa
e-mail: mwadham.kabanda@nwu.ac.za
Material Science Innovation and Modelling (MaSIM) Research Focus Area,
Faculty of Natural and Agricultural Sciences, North-West University,
Private Bag X 2046, Mmabatho 2735, South Africa
© Springer Nature Switzerland AG 2020
L. Mammino et al. (eds.), Advances in Quantum Systems in Chemistry,
Physics, and Biology, Progress in Theoretical Chemistry and Physics 32,
https://doi.org/10.1007/978-3-030-34941-7_7
119