Letters in Organic Chemistry - Volume 12, Issue 4, 2015

In this paper, some benzimidazole derivatives containing salicyl, oxadiazole, thiosemicarbazide and 1, 2, 4-triazole moieties have been synthesized and screened their antioxidant activities screened. Antioxidant activities of the synthesized compounds were tested with DPPH and ABTS•+ radical cation decolorization assays. Compounds 4b, 6a, 6b, 7a and 7b showed very good scavenging activity.

The aromaticity index D ={[π1+∑2n (π1 – π 2 )]0 / [π1+∑2n (π1 – π 2 )]}× a , where π1 ... πn are the energy of the occupied molecular orbitals and a is the number of the cycles in the molecule, has been tested in the case of substituted hexaatomic aromatic compounds. The correlation between D and ASE in the case of substituted benzene derivatives is reported. Furthermore, the correlations between D and ISE in the case of substituted naphthalene and pyridine derivatives showed a good correlation.

A convergent and facile synthesis of thiourea-based novel 1-(3-nitrophenyl)-3-(7- (substituted phenylamino/piperazino)quinolin-4-yl)thiourea derivatives is presented by approaching copper catalyzed Ullmann reaction. Pliable route was adopted to achieve amination on bioactive 4,7- dichloroquinoline analogous for the first time in which substituted amine/piperazine condensed with C-7 position of quinoline core. Presented C-N coupling reaction precedes fair to good yields. Cu(0) catalyzed synthetic route was also explained by discussing its probable mechanism. On the basis of currently available antimicrobial drugs, we rationalized the title compounds and examined their biological potency. Compound 3i proved to be the most potent antimicrobial derivative (36 mm, 0.39 μg/mL MIC) against B. cereus strain than standard Ciprofloxacin (31 mm, 0.39 μg/mL MIC). Compound 4e showed equipotent antituberculosis (99% inhibition, 6.25 μg/mL MIC) effect against H37Rv strain as compared to Pyrazinamide. Final analogues were characterized by IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analysis.

The synthesis and cytotoxicity evaluation of fourteen new chalcones containing 5-fluorouracil were introduced in which nine chalcones as Mannich bases 8a-i were synthesized from 2'-hydroxyacetophenone (1) in three steps including chloromethylation, N-alkylation and Claisen-Schmidt reactions. Other chalcones 14a-e were obtained from Click reaction between 1,3-dipropargyl-5-fluorouracil and azide derivatives of 2',4'-dihydroxychalcone. The bio-assay results showed that 11 chalcones (excluding 8d, 8f and 8h) exhibited cytotoxicity against four human cancer cell lines including Hep-G2, RD, LU-1 and FL in which compound 14e exhibited the most potent cytotoxicity against Hep-G2, RD, LU-1 and FL with IC50 values of 1.48, 10.59, 3.64 and 7.02 μg/mL, respectively.

Although viewed as promising drug candidates, few efforts have been addressed towards the structural chemistry of 2-hydrazonothiazolidin-4-ones. Therefore, 2-[(3-phenylsulfanylpropylidene)- hydrazono]thiazolidin-4-one (ATZ3) was synthesized and its crystal and molecular structure was studied by NMR and X-ray single crystal diffraction. The 1H NMR spectral data indicated that the hydrazone group assumes the Econfiguration, which was further confirmed by bi-dimensional NMR and crystallographic data. Despite agreement between most bond lengths and angleswith their expected values, the crystalline packing provided important information with regard to the double bond position involving the C-4 carbon. Quantum chemical calculations at Semiempirical, Density Functional Theory (DFT) and Ab Initio levels provided a good agreement between calculated and structural results provided by X-ray analysis. The system’s dimerization energies were also estimated. Statistical and Hierarchic Cluster Analysis (HCA) revealed interesting aspects of the calculations and pointed to the B3LYP as the most accurate in the determination of structure among the methods considered, in spite of some good results achieved by semiempirical schemes.

Sodium benzenesulfinates, as a new organo catalyst, can be used to synthesize tetrahydro- 4H-chromene derivatives by three component reaction of cyclic β-dicarbonyl compounds, malononitrile, and aromatic aldehydes, in H2O/EtOH, under ultrasound irradiation at room temperature. Inexpensiveness, stability and the potential of being easily obtained can be noted as preponderance of these catalysts. Furthermore, high conversions, short reaction times and cleaner reaction profiles are some of the advantages of this method. Moreover, H2O/EtOH (7:3) was selected as a green solvent.

An improved method for the synthesis of 3-quinuclidinone hydrochloride 4 from piperidine-4-carboxylic acid 1 has been described. Reaction of piperidine-4-carboxylic acid 1 with thionyl chloride and ethanol gave ethyl piperidine 4-carboxylate 2. It was further condensed with methyl chloroacetate in presence of sodium carbonate to give ethyl 1-(2-methoxy-2- oxoethyl)piperidine-4-carboxylate 3. One pot Dieckmann reaction of 3 in presence of potassium tertbutoxide followed by hydrolysis and decarboxylation gave title compound azabicyclo[2.2.2]oct-3-one hydrochloride 4.

A practical phosphotungstic acid-catalyzed aromatic transesterification reaction for the preparation of aryl benzoates has been developed. The transesterification method avoids the oxidation of the corresponding phenols to quinone compounds with easy operations, environmentally benign conditions and high yields of the products. It is noteworthy that in this process phosphotungstic acid can be reused and recycled.

In search of novel potent bioactive compounds, a series of novel maleimide-based thiourea derivatives containing terpinene structure were designed and synthesized. Their structures were characterized by IR, MS, NMR, UV-vis and elemental analysis. The preliminary bioassay showed that the target compounds exhibited a certain fungicidal activity, in which compound 2-methoxyphenyl-Naminoethyl- terpinene-maleimide-based thiourea 5h exhibited the best inhibitory ratio of 64.2% against Alternaria solani at the concentration of 50 μg•mL-1. A few of the target compounds showed a certain growth inhibition activity against rape root (Brassica campestris), in which compound 5h exhibited the best inhibitory ratio of 82.0% (A-class activity level) at the concentration of 100 μg•mL-1. The intermediate 4 exhibited excellent growth inhibitory ratio of 92.3% (A-class activity level) against rape root at the concentration of 100 μg•mL-1. In addition, the structureantifungal activity relationship of these compounds was also discussed.

A green, efficient and operationally simple method for three-component synthesis of 1,2,3- trisubstituted pyrrole derivatives via an iodine-catalyzed tandem reaction has been developed, and a series of 1,2,3-trisubstituted pyrrole derivatives were synthesized from simple starting materials under neutral conditions, with good to excellent yields in short time. This method showcased the potential of great value as a mild, rapid, and general procedure for the synthesis of 1,2,3-trisubstituted pyrroles.