Letters in Organic Chemistry - Volume 18, Issue 7, 2021

Orexin has been emerged as a hot and frontier research theme in the close relationship with sleep-wake regulation. In this paper, we report a synthetic method for the preparation of 5-methyl-2- (pyrimidin-2-yl)benzoic acid, which is an important molecular fragment of orexin Filorexant (MK- 6096). Compared to the previously reported methods, the current route has the advantages of a short synthetic pathway, simple post-treatment, and high yield that provide an effective new methodology for the synthesis of the target compound. Using 2-bromo-5-methyl benzoic acid and 2- chloropyrimidine as raw materials, PdCl2(PPh3)2 is used as a metal catalyst to mediate one-pot generation of 5-methyl-2-(pyrimidin-2-yl)benzoic acid using the Negishi cross-coupling method. The optimum condition involves 2-bromo-5-methylbenzoic acid (10.00 g) and anhydrous zinc chloride powder (6.32 g) together with the catalyst: 2-bromo-5-methylbenzoic acid molar ratio of 0.02 and 2- chloropyrimidine: 2-bromo-5-methylbenzoic acid molar ratio of 1.1:1 at a reaction temperature of 55°C for 14 h. Under these optimum reaction conditions, the maximum yield of 78.4% is attained for 5- methyl-2-(pyrimidin-2-yl) benzoic acid.

Oceans can play a major role in supplying life-saving medicines to the world. Although considerable progress has been made in finding new medicines from marine sources, great efforts are still necessary to examine such molecules for clinical applications. Xyloketals are an important group of natural products with various powerful and prominent bioactivities such as inhibition of acetylcholine esterase, antioxidant activity, inhibition of L-calcium channels, radical-scavenging behavior, suppression of cell proliferation, reduction of neonatal hypoxic-ischemic brain injury, etc. This review describes the isolation and structural characterization of all xyloketal natural products giving major emphasis on their bioactivity.

In the present paper, a simple, highly efficient, and environmentally friendly protocol was proposed for the Knoevenagel condensation reaction of aromatic aldehydes using Meldrum’s acid (2,2-dimethyl-4,6-dioxo-1,3-dioxane) with bentonite as an available non-toxic mineral catalyst exposed to aqueous media under green conditions. Together with the substitution protocol of electron-donating or -withdrawing groups, all reactions were finalized from 5 to 120 min in water at 90°C. With regard to such reactions, the purification of columns on products was not a requirement. Considering the environmental aspect, use of water as a green solvent, utilization of a reusable catalyst, simple work-up process and steps, as well as rapid reaction times were taken into account as some characteristics of these chemical reactions.

The conventional Biginelli synthesis is more cumbersome and produces lower yields. Several improved methods are reported in the literature to replace the Biginelli catalyst. The design of biocompatible organic transformation is a major concern and a versatile greener procedure to construct Biginelli analogs is in great demand. Factorial design guided, energy-efficient, and versatile synthesis of 3,4-dihydropyrimidin-2-(1H)-ones (DHPM) was developed. One-factor-at-a time (OFAT) and factorial design (2³) studies were utilized for screening the independent variables. The optimum levels of potential variables (benzyl-n-triethylammonium chloride (BTEAC) and glacial acetic acid) were determined through studies. The factorial design (3²) analysis inferred the use of BTEAC (10.25 mol%) and glacial acetic acid (7.6 ml) as optimal for the 60 min condensation. Thirteen new 3,4- dihydropyrimidine-2-(1H)-one (DHPM) analogs were synthesized using optimized reaction conditions. The quaternary ammonium ion of BTEAC stabilizes the polarization of carbonyl group in aryl aldehydes and enolizable ketone (alkyl acetoacetate) to facilitate the cyclocondensation, in order to produce DHPMs through N-acyliminium ion and Michael adducts formation. The biocompatible strategy, simple product isolation (non-chromatographic method), and good to excellent yields are attractive features of this new protocol. Hence, the newly developed methodology is superior to the literature methods.

An expeditious and operationally simple reaction between 3-hydrazonobutan-2-one oxime and different substituted benzaldehydes in the presence of silica afforded an unexpected product, biacetyl bis-hydrazone Schiff bases in good yield on grinding in a mortar at room temperature, instead of expected product 3-(aryl)methylenehydrazonobutan-2-one oxime. Mild reaction conditions involving recyclable mineral support silica, environmentally benign and good yield in short reaction time are remarkable advantages of this protocol. Products were characterized by IR, NMR (¹H and ¹³C) and elemental analyses.

In this paper, a novel series of 1-(alkyl)-3-(2-oxo-2H-chromenyloxy acetamido) methylpyridinium salts were synthesized in a simple and efficient way. The method showed to be facile and the compounds were obtained in high isolated yields. All the synthesized compounds were characterized by ¹H NMR, ¹³C NMR, FT-IR, Mass and elemental analysis. AChE and BuChE inhibition activity of the synthesized compounds were evaluated and the results showed that all the compounds were active in the inhibition of the mentioned enzymes. All the compounds were active in the inhibition of the two studied enzymes. Among all the compounds, the compound 6a (1.85 μM) and 6i (0.106 μM) showed the highest inhibition activity against AChE and BuChE, respectively. The kinetic study was performed to get more insight into the mechanism of action of the synthesized compounds. Docking studies were also performed to obtain the interactions between the synthesized compounds and the enzymes.

The present investigation aimed to synthesize quinazoline-4(3H)-one derivatives (B1-10) and evaluated their antimicrobial activity. The test compounds (B1-10) were obtained by reaction of 2- phenyl-4H-benzo[d] [1, 3]oxazin-4-one (1) with 4-aminophenol (2) to afford 3-(4-hydroxyphenyl)-2- phenylquinazoline-4(3H)-one (3) which were further reacted with different N-phenylacetamide (4) in the presence of anhydrous potassium carbonate and a catalytic amount of potassium iodide in ethylmethylketone. The test compounds (B1-10) were characterized by the spectroscopic method and evaluated for their antimicrobial activity using the cup plate method by measuring the zone of inhibition. Among the compounds, compound B1, B2, B4, B6, and B8 showed maximum zone of inhibition as compared to standard drug ciprofloxacin and fluconazole against Bacillus subtilis, Escherichia coli and Aspergillus niger. Molecular docking was also performed for test compounds to predict their binding affinities in the target protein and results showed good drug-like properties.

A series of new thiouracil compounds containing 1,2,4-triazolo[1,5-a]pyrimidine were designed and synthesized. The in vitro antibacterial activities of the new compounds against Bacillus amyloliquefaciens, Staphylococcus aureus and Bacillus subtilis were tested. The results showed that some of the new compounds had strong inhibitory activities against the tested bacteria. At the concentration of 50 μg/mL, the compound 12d had broad and the highest inhibitory activity with the 100% inhibition against the three tested strains, the same as norfloxacin which was used as the control.

Fe3O44 magnetic nanoparticles (MNPs) were prepared via a chemical co-precipitation method. Then, the surface of Fe3O44 MNPs was modified by (3-Chloropropyl)trimethoxysilane and then two Schiffbase complexes of zirconium oxide and copper were stabilized on modified Fe3O44 MNPs. These catalysts were characterized using SEM, EDS, WDX, FTIR, XRD, TGA, VSM and AAS techniques. The catalytic activity of these catalysts was described in the carbon-carbon coupling reaction. VSM analysis of these catalysts indicates the high magnetic performance; therefore these catalysts can be recovered by an external magnet and reused several times without reducing the number of catalysts. Reusability, excellent yields and high TON values indicate the high efficiency of these catalysts. Leaching of these catalysts was studied by AAS which leaching of copper or zirconium was not observed. Also, the stability of these catalysts was confirmed by the characterization of recovered catalysts and comparing to fresh catalysts.

A series of substituted imidazole-pyrazole fused compounds were designed & fused synthesized by employing Debus-Radziszewski one-pot synthesis reaction. Azoles are an extensive and comparatively new class of synthetic compounds including imidazoles and pyrazoles. The current clinical treatment uses compounds of azole framework. Azoles act by inhibiting ergosterol synthesis pathway (a principal component of the fungal cell wall). In addition, a literature review shows that the compounds that include imidazoles and pyrazoles have significant anti-bacterial and anti-mycobacterial effects. In light of the above findings, a series of compounds with imidazole and pyrazole scaffolds were sketched and developed to examine anti-bacterial, antifungal and antimycobacterial activities. The structures of the synthesized compounds were characterized using ¹HNMR, ¹³CNMR, elemental analysis, and MS spectral data. The target compounds were screened for their in-vitro antimicrobial activity against gram-positive and gram-negative bacterial species by disc diffusion method according to the NCCLS (National Committee for Clinical Laboratory Standards) and anti-mycobacterial activity against the Mycobacterium tuberculosis H37Rv strain. The results revealed that imidazole-pyrazole fused scaffold compounds have potential antibacterial, antifungal and anti-mycobacterial activities which can be further optimized to get a lead compound.