Synthesis of Urea and Hydantoin Derivatives and Their Antibacterial Properties

Chang, Wei Jin (2023) Synthesis of Urea and Hydantoin Derivatives and Their Antibacterial Properties. Final Year Project (Bachelor), Tunku Abdul Rahman University College.

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Abstract

In this project, 3-substituted hydantoins (4 examples with yields from 32 % to 99 %) were synthesized using the Gabriel synthesis by alkylation of hydantoin under basic ambient conditions, whereas urea derivatives were synthesized from primary amines and potassium cyanate (7 examples with yields from 18 % to quantitative) under acidic ambient conditions. Notably, N,N-(diethylaminopropyl)urea (Urea 6) is a newly-reported urea derivative. The synthesized organic products were isolated and characterized using Fourier-transform Infrared Spectroscopy (FTIR), proton and Carbon-13 Nuclear Magnetic Resonance (1H, 13C NMR), and Differential Scanning Calorimetry (DSC). The efficiencies and effect of the substrates on the Gabriel synthesis and urea derivatives synthesis were analysed and discussed. Selected hydantoin and urea derivatives were screened for antimicrobial activity against Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) using the Kirby Bauer disc diffusion method. Furthermore, a novel synthesis pathway to access substituted hydantoins by coupling the urea derivatives to alpha-bromoester and cyclizing the resulting ureido intermediates was investigated. Lastly, a novel, facile and solvent-free synthesis pathway to the phase transfer catalyst, tetrabutylammonium bromide (TBAB) involving consecutive alkylation steps of n-butylamine with 1-bromobutane, was carried out for the urea derivative coupling reaction in this work. The significance of this study would be to explore the novel synthesis pathway to the hydantoin scaffold using urea derivatives as the starting material