Synthesis of some 1H-1,5-benzodiazepine Series Containing Chromene Ring from α,β-Unsaturated Ketones of 6-Acetyl-5-Hydroxy-4-Methylcoumarin

Abstract

Background: Reaction of α,β-unsaturated ketones with o-phenylenediamine afforded corresponding 2,3-dihydro-1H-1,5- benzodiazepines. Objective: α,β-Unsaturated ketones of 6-acetyl-5-hydroxy-4-methylcoumarin were precursors for synthesis of 2,3-dihydro1H-1,5-benzodiazepines through its reaction with o-phenylenediamine. Method: Enones of 6-acetyl-5-hydroxy-4-methylcoumarin were prepared from this ketone and (un)substituted benzaldehydes in the presence of piperidine, triethylamine, or pyridine as a catalyst in absolute ethanol with 1:1 molar ratios, respectively. 2ʹ,3ʹ-Dihydro-1H-1ʹ,5ʹ-benzodiazepines were synthesized by using the reaction of these enones with o-phenylenediamine in absolute ethanol in the presence of with glacial acetic acid as a catalyst. Their biological activities were evaluated using disk diffusion method. Method: Enones of 6-acetyl-5-hydroxy-4-methylcoumarin were prepared from this ketone and (un)substituted benzaldehydes in the presence of piperidine, triethylamine, or pyridine as a catalyst in absolute ethanol with 1:1 molar ratios, respectively. 2ʹ,3ʹ-Dihydro-1H-1ʹ,5ʹ-benzodiazepines were synthesized by using the reaction of these enones with o-phenylenediamine in absolute ethanol in the presence of with glacial acetic acid as a catalyst. Their biological activities were evaluated using disk diffusion method. Results: Seven new 2ʹ,3ʹ-dihydro-1H-1ʹ,5ʹ-benzodiazepines were obtained and their structures were confirmed by thin layer chromatography, IR, NMR and MS spectra. Some synthesized benzodiazepines had antibacterial and antifungal activities againsts Escherichia coli (Gram-(−) bacterium), Staphylococus epidermidis (Gram-(+) bacterium). Candida albicans (fungus). Conclusion: The formation of enones from 6-acetyl-5-hydroxy-4-methylcoumarin and (un)substituted benzaldehydes could be catalyzed by piperidine, triethylamine, pyridine to afford the similar yields. The formation of 2ʹ,3ʹ-dihydro-1H-1ʹ,5ʹbenzodiazepine structure from the aforementioned enones and o-phenylenediamine.

Design, synthesis, molecular docking study and molecular dynamics simulation of new coumarin-pyrimidine hybrid compounds having anticancer and antidiabetic activity

“…Reaction yields achieved to 48–78%. As has been mentioned in our previous articles [ 25 , 26 ], several other organic bases can also be used in this condensation reaction, such as trimethylamine and pyridine, and the same yields were obtained with the similar reaction time. On the other hand, strong inorganic bases, such as NaOH and KOH, gave lower yields of target α,β-unsaturated ketones 5a–h due to the ring opening of 2 H -pyran-2-one component of coumarin under these strong base conditions, although these alkaline hydroxides have been successfully applied during the synthesis of other aromatic α,β-unsaturated ketones from aromatic aldehydes and ketones.…”

“…This process was carried out in the presence of AlCl 3 as Lewis acid catalyst in nitrobenzene. Initial materials for synthesis of pyrimidine ring, i.e., α,β-unsaturated ketones 5a–h , were prepared by using Claisen-Schmidt condensation reaction of ketone 3 with some different aromatic and heteroaromatic aldehydes 4a–h according to our previous procedure (Scheme 1 ) [ 25 ]. Molar ratio of 3 and 4a–h was 1:1.…”

“…Other functional groups in compounds 5a–h also characterized by spectral data. Phenolic-hydroxyl group on position 5 of coumarin ring had IR absorption band at 3450–3245 cm –1 as well as chemical shifts at δ = 15.32–14.94 ppm in their 1 H NMR [ 25 ]. Lactone carbonyl group in 2 H -pyran-2-one component had IR absorption band at 1755–1682 cm –1 , whereas IR absorption band at 1651–1622 cm –1 belonged to carbonyl group conjugated to benzene ring of coumarin and alkene carbon-carbon bond in position α.…”

“…Successful construction of pyrimidines ring 6a–h having coumarin component from α,β-unsaturated ketones 5a–h and guanidine was determined by IR and NMR spectral data. In the IR and 1 H NMR spectra there were not any absorption characteristics for trans -alkene double bonds as mentioned above, as well as the resonant signal of ketone carbon in the region of δ~193.1 ppm in 13 C NMR spectra [ 25 ]. Amino group at position 2 of pyrimidine ring was characterized by two IR absorption bands that appeared in regions at 3345–3293 and 3232–3196 cm –1 .…”

Synthetic aspects of 1,4- and 1,5-benzodiazepines usingo-phenylenediamine: a study of past quinquennial

“…Toan et al 55 synthesized some 1 H -1,5-BZDs (5) containing a chromene ring using OPD (1) and α,β-unsaturated ketone (5-hydroxy-4-methyl-6-[(2 E )-3′-(aryl)-prop-2′-enoyl]-2 H -chromen-2-ones) (4) in the presence of glacial acetic acid as a catalyst and ethanol as a solvent. This ketone (4) was prepared from 6-acetyl-5-hydroxy-4-methylcoumarin and aldehyde with piperidine/TEA (triethylamine)/pyridine as a catalyst in ethanol.…”