AIMS The aim of the present research was to synthesize glycoluril derivative 2,4-Bis(4- cyanobenzyl)glycoluril through a 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 1HNMR, 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 the newly synthesized compound and thiourea were determined by using density functional theory. RESULTS Furthermore, the compound was evaluated against urease enzyme and was found to be potent inhibitors with an IC50 value of 11.5 ± 1.50 μM when compared with standard inhibitor thiourea (IC50 = 21.0 ± 1.90 μM). The compound may serve as a lead compound to synthesize new cyano-based bambusuril in the 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 been 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 the future. The yield of the obtained product has been monitored by using different amounts of cyanating reagent, but the best results are shown by the use of 4 mmol of CuCl/KCN. KCN with CuCl assisted the conversion of diazo group into the cyano group with enhanced yield when used in excess amount. It acts as a catalyst. The solubility characteristic of 2,4-Bis(4-cyanobenzyl)glycoluril has also been determined 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 the presence of CN group near the benzylic protons. Methine protons show a signal at 5.2 ppm, which ensures 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 inhibition, which is in good agreement with the experimental data.

中文翻译：

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使用 Sandmeyer 反应和密度泛函理论研究合成脲酶抑制剂 2, 4-双（4-氰基苄基）甘脲。

目的本研究的目的是通过收敛方案合成甘脲衍生物2,4-双(4-氰基苄基)甘脲。背景技术为此目的，Sandmeyer反应程序被用于合成所述化合物。通过使用不同的光谱技术，如 1HNMR、13C-NMR 和 (HR-MS) 质谱法确认了纯化合物的结构。目的 使用 SANDMEYER 反应和脲酶抑制研究来聚合合成 2,4-BIS（4-氰基苄基）甘脲。方法通过1​​H-NMR、13C-NMR和(HR-MS)质谱等不同的光谱技术对纯化合物的结构进行了确认。新合成的化合物和硫脲的电子性质是通过使用密度泛函理论确定的。结果 此外，该化合物针对脲酶进行了评估，发现与标准抑制剂硫脲 (IC50 = 21.0 ± 1.90 μM) 相比，它是有效的抑制剂，IC50 值为 11.5 ± 1.50 μM。该化合物未来可作为先导化合物合成具有增强生物特性的新型氰基竹苏里。结论我们通过sandmeyer反应合成了一种新的甘脲衍生物2,4-双(4-氰基苄基)甘脲。它以淡黄色粉末的形式以良好的收率 (96%) 获得。基于甘脲的大环化合物已用于各个领域；从 2,4-双（4-硝基苄基）甘脲（已经报道的化合物）开始，它分别经历了还原（CH3OH,Pt/C）、重氮化（NaNO2/HCl）、氰化（CuCl/KCN），以便合成所需的新甘脲衍生物。所得产物未来将用作合成氰基竹苏里大环的基石。已通过使用不同量的氰化试剂监测所得产物的产率，但使用 4 mmol CuCl/KCN 显示出最佳结果。当过量使用时，KCN 与 CuCl 有助于重氮基团转化为氰基，并提高产率。它充当催化剂。2,4-双（4-氰基苄基）甘脲在不同有机溶剂中的溶解度特性也已确定。1H NMR 技术被证明对我们所需产品的结构测定非常有帮助。苄基质子分别在 7.5 ppm 和 7.8 ppm 处发出信号。低场峰证实了在苄质质子附近存在 CN 基团。次甲基质子在 5.2 ppm 处显示信号，这确保了甘脲的基本骨架。脲基质子也证实了杂环 2,4-双（4-氰基苄基）甘脲化合物的合成。前沿分子轨道的负和正静电势位点、分子描述符和电荷密度分布表明，具有亲电和亲核攻击有希望的位点的 4a 将导致增强脲酶抑制，这与实验数据非常吻合。