Synthesis, Characterization of Substituted 1,3-Oxazepine, Thiazolidine-4-one and Azetidine-2-one Using Benzimidazole as a Synthon

Starting from benzimidazole moiety, several heterocyclic compounds (1,3-Oxazepine, thiazolidin-4-one, azetidin-2-one) were synthesized, thus the Ethyl Benzimidazole acetate (1) was synthesized from the reaction of benzimidazole with ethylchloroacetate on treatment with hydrazine hydrate is giving the corresponding hydrazide (2). The reaction of this hydrazide with, 4-substituted acetophenone afforded hydrazones which on reaction with some reagents to produce synthesized compounds, (4a-c), (5a-c), (6a-c), (7a-c), (8a-c) and (9a-c). All the synthesized products were confirmed by physical and spectral methods.


INTRODUCTION
Due to its wide range of biological activities, including antibacterial, antitubercular, anticancer, anticonvulsant, and antifungal properties, the derivatives of the thiazolidin-4-one nucleus have taken a special place in the field of medicinal chemistry (Christophe et al., 2022;Pandurangan et al., 2022). Azitidine-2-one are heterocyclic compounds frequently found in compounds of biological interest, and have been shown to exhibit a wide range of biological activities (Maria et al., 2020). The pharmacophore of lactam antibiotics, the most commonly used family of antibiotics, is well established as the azetidine-2-one skeleton (Trivedi et al., 2008). Properly substituted azitidine synthesis techniques have been developed with control of functional group and stereochemistry through the structural diversity of physiologically active β-lactam antibiotics (Hanoon et al., 2021). The 1,3-oxazepine is heterocyclic ring and contains two heterocyclic atoms (oxygen and nitrogen) (Tong, 2013), which have been found to exhibit biological activities (Maysaa and Moayed, 2022). The identification of 1,3-oxazepine's CNS action (Deng et al., 2016).

EXPERIMENTAL Instrumentation
The uncorrected melting points were all calculated using Thiel's tube At Kirkuk University/ College of Science/ Department of Chemistry. Using a Bruker Model Tensor 27 Co., Germany spectrophotometer, infrared spectrums were captured At the University of Baghdad/ Central Service Research Center/ Ibn Al-Haytham. Chemical shifts were expressed in parts per million (ppm) downfield from TMS using the proton resonance magnetic spectra ( 1 H-NMR and 13 C-NMR) recorded on a 400MHz spectrophotometer using TMS as an internal standard At the University of Isfahan/ Central Laboratories/ Islamic Republic of Iran. The elemental analysis was carried out by using EA Euro vector 3000 element analyzer At Al-Bayt University/Water Research Center/The Hashemite Kingdom of Jordan. Thin layer chromatography (TLC) was used to monitor the reaction's progress and product purity. Iodine fumes were present where the spots were.

Synthesis of Ethyl benzimidazole acetate (1)
The solution of Benzimidazole (0.06 mole) in acetone (40 ml) was mixed with 0.07 moles of ethyl chloroacetate and 0.12 mole of potassium carbonate, and the mixture was refluxed for six hours this reaction was monitored by TLC, the reaction mixture was filtered, and excess acetone was then distilled out of the clean filtrate before water was added. The separated solid product was filtered, collected, and dried. Ethyl acetate crystallization was used to provide further purification Afforded solid as white color M.P. 88-90 °C, yield 86%, as well as identification of the ester (1) by using chemical detectors, the detection test known as (Ferric hydroxamate) give positive result, which denotes the existence of ester (John et al., 1986;Gowda et al., 2010).

Synthesis of Benzimidazole acetic acid hydrazide (2)
The solution of ethyl benzimidazole acetate (1) (0.04 mole) in ethanol (25 ml) was mixed with hydrazine hydrate (99%) (0.04 mole) and refluxed for (4hr), completion of the reaction was monitored by TLC, the excess of solvent was removed by distillation and the contents were added to an excess of water. The crude product was purified by recrystallization from ethanol to give grey precipitate M.P. 180-181 °C, Yield 90%, (Gowda et al., 2010).

Synthesis of 4-substituted acetophenone (3a-c)
A mixture of 4-amino acetophenone (0.01 mole) in (50 ml) ethanol, and succinic anhydride or maleic anhydride or phthalic anhydride (0.01 mole). Reflux heating was used to warm the reaction mixture for (3 hr). TLC was performed after the reaction, and then the reaction mixture was allowed to cool, the precipitate was filtered and recrystallized from ethanol. The properties of compounds show in the (Table 1)

RESULTS AND DISCUSSION
The compounds (3a-c) were preparation from the reaction 4-amino acetophenone with maleic anhydride or succinic anhydride or phthalic anhydride in ethanol absolute, As shown in scheme I, and also shown in mechanism.