Aims:
The aim of present research was to synthesize glycoluril derivative 2,4-Bis(4-cyanobenzyl)glycoluril through convergent
scheme.
Background:
For this purpose Sandmeyer reaction procedure was employed for the synthesis of said compound. The structure of the pure
compound was confirmed by using different spectroscopic techniques such as 1H-NMR, 13C-NMR and (HR-MS) Mass spectrometry.
Objective:
Convergent synthesis of 2,4-BIS (4-CYANOBENZYL)GLYCOLURIL USING SANDMEYER REACTION and urease inhibition
study.
Methods:
The structure of the pure compound was confirmed by using different spectroscopic techniques such as 1H-NMR, 13C-NMR and
(HR-MS) Mass spectrometry. The electronic properties of newly synthesized compound and thiourea were determined by using density
functional theory.
Results:
Furthermore compound was evaluated against urease enzyme and was found to be potent inhibitors with IC50 value of 11.5 ± 1.50
µM when compared with standard inhibitor thiourea (IC50 = 21.0 ± 1.90 µM). Compound may serve as lead compound for the synthesis of
new cyano based bambusuril in future with enhanced biological properties.
Conclusion:
We have synthesized a new glycoluril derivative 2,4-Bis(4-cyanobenzyl)glycoluril by the sandmeyer reaction. It has obtained in
the form of light yellowish powder in good yield (96%). Glycoluril based macrocycles have been used in various fields. Starting from the
2,4-Bis(4-nitrobenzyl)glycoluril (already reported compound) which has undergone reduction (CH3OH,Pt/C) , diazotization (NaNO2/HCl),
cyanation (CuCl/KCN) respectively in order to synthesize the desired new glycoluril derivative. The obtained product will be used as a
building block for the synthesis of the cyano based bambusuril marcocycle in future. The yield of the obtained product has been monitored
by using different amount of cyanating reagent but the best results shown by the use of 4 mmol of CuCl/KCN. KCN with CuCl assisted the
conversion of diazo group into cyano group with enhanced yield when used in excess amount. It act as a catalyst. Solubility characteristic of
2,4-Bis(4-cyanobenzyl)glycoluril has determined also in different organic solvents. 1H NMR technique proved to be very helpful for the
structure determination of our desired product. Benzylic protons give signals at 7.5 ppm and 7.8 ppm respectively. The downfield peaks
confirm about the presence of CN group near the benzylic protons. Methine protons show signal at 5.2 ppm which ensures about the basic
skeleton of glycoluril. Ureidyl protons also confirm the synthesis of the heterocyclic 2,4-Bis(4-cyanobenzyl)glycoluril compound. The
negative and positive electrostatic potential sites, molecular descriptors, and charge density distribution of frontier molecular orbitals are
revealing that 4a with promising sites for electrophilic and nucleophilic attacks would result to enhance the urease inhbition which is in good
agreement with the experimental data.
Can ion mobility mass spectrometry and density functional theory help elucidate protonation sites in 'small' molecules?
