Band 19, Heft 1

Heterocyclic compounds are of immense interest due to their extensive occurrence in nature as well as their applicability in the pharmaceutical industry. Benzothiazole and its derivatives encompass an attractive heterocyclic class that displays practical applications ranging from mevdicine to photography and agriculture, among other things. This review focuses on the synthesis and specific applications of various benzothiazole cyanine dyes. Benzothiazole-containing heterocyclic structures are prominent throughout the literature and it is very important to acknowledge their efficacy and applicability as we discuss herein.

A review focused on our contributions to the synthesis and chemistry of hexasubstituted pyrazolines is presented. The development of a synthetic route to pentasubstituted 2 H -pyrazoles 1 provides the key starting materials that are used in the synthesis of several unique series of highly substituted pyrazolines 2–6 . Thermolysis of pyrazolines 2–4 allows the facile synthesis of hexasubstituted cyclopropanes. Autoxidation of pentasubstituted 2 H -pyrazoles 1 in acetone produces a series of hydroperoxy substituted pyrazolines 5 which are effective oxygen-atom transfer reagents. The thermal decomposition of 5 produces β-keto radicals, the transformation of which in the presence of oxygen provides a good route for the synthesis of 3-hydroxy-1,2-dioxolanes. The reaction of tosyl chloride with a pentasubstituted 2 H -pyrazole yields a chloro-substituted pyrazoline 6 rather than the expected N -tosyl product. Thermolysis of 6 yields products, the structure of which is consistent with the formation of an unstable intermediate chloro-substituted cyclopropane.

A series of 2-pyridylthio and 2-pyrimidinylthio derivatives of calix[4]arene have been synthesized and characterized by IR, 1 H NMR, 13 C NMR and MS.

A number of chalcones bearing an oxazole cycle were synthesized by Claisen-Schmidt condensation of 5-acetyl-2(3 H )-benzoxazolone or 6-acetyl-2(3 H )-benzoxazolone and the appropriate aldehydes. The chalcones were evaluated for cytotoxic activity against several tumor cell lines – BV-173 (human B cell precursor leukemia), MCF-7 and MDA-MB-231 (human breast adenocarcinoma) using the MTT-dye reduction assay. The tested compounds exhibit concentration-dependent cytotoxic effects at micromolar concentrations. Exposure of the BV-173 tumor cell line to compound 3f results in strong mono- and oligonucleosomal fragmentation of genomic DNA, as evidenced by a ‘cell death detection’ ELISA kit, which unambiguously indicates that the induction of apoptosis is implicated in the cytotoxic mode of action of the tested compound.

A series of new benzofuran derivatives 3a–f , 5a–e containing a heterocyclic substituent linked to benzofuran nucleus at C-2 were synthesized as potential antitumor agents. These products were synthesized starting with 2-bromoacetylbenzofuran 1 . The structures of all compounds were established on the basis of analytical and spectral data. The synthesized compounds were tested against human liver carcinoma cell line (HEPG2) and all were more potent than the comparative standard (5-flurouracil). Compound 3f was the most active (IC 50 = 12.4 μg/mL).

In recent years, synthesis and biological evaluation of novel 4 H -1,4-benzothiazines and their sulfone derivatives have gained momentum due to their medicinal and industrial importance. Our studies focused on the design and synthesis of new antimicrobial agents, and for this purpose a series of novel 4 H -1,4-benzothiazines and their sulfone derivatives were synthesized and their in vitro antimicrobial assessment was carried out against a representative panel of Gram-positive and Gram-negative bacteria strains and selected fungi species. The reported 4 H -1,4-benzothiazines were prepared by condensation followed by oxidative cyclization of substituted 2-aminobenzenethiols with compounds containing active methylene groups. It is believed that the reaction proceeds via intermediary of the enaminoketone system. The sulfone derivatives were synthesized by oxidation of 4 H -1,4-benzothiazines using 30% hydrogen peroxide in glacial acetic acid. Structure determination was done by spectral and elemental investigations.

Condensations of thiosemicarbazones 1 derived from 1-tetralones with chloroacetic acid and 2-bromopropionic acid in the presence of N -methylpyridinium p -toluenesulfonate (an ionic liquid) yield the corresponding 2-substituted 4-thiazolidinones 2 . The reactions of 1 with 3-chloropropionic acid afford perhydro-1,3-thiazinan-4-ones 3 in excellent yields. The structures of compounds 2 and 3 were established on the basis of elemental analysis, IR, NMR and mass spectral data. X-Ray crystallographic studies of compound 2a are reported. Compounds 1–3 were investigated for antimicrobial activities against Bacillus subtilis, Staphylococcus aureus (Gram-positive bacteria) and Pseudomonas aeruginosa, Escherichia coli (Gram-negative bacteria) and the fungi Aspergillus niger, Candida albicans and Aspergillus fumigatus . Thiazolidin-4-ones were found to be more active than perhydrothiazin-4-ones.

The reaction of hydrazide 4 with β-keto esters 5 gave hydrazones 6 . Cyclization of 6 with Vilsmeier-Haack reagent (DMF-POCl 3 ) for 20 min at room temperature gave 1-(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-1 H -pyrazole-4-carboxylic acid ethyl esters 7 . The treatment of 4 with substituted acetophenones 8 yielded the corresponding hydrazones 9 of substituted acetophenones. The treatment of 9 with Vilsmeier-Haack reagent (DMF-POCl 3 ) for 30 min at room temperature gave product 10 , the reaction of which with (diacetoxyiodo)benzene in ethanol at room temperature for 12 h in the presence of molecular iodine furnished 7 .

A convenient and practical synthesis of 1,8-dioxo-decahydroacridine derivatives using various aldehydes, 5,5-dimethyl-1,3-cyclohexanedione and thiourea in water, was successfully carried out in the presence of melamine-formaldehyde resin supported H + (MFRH) as a catalyst. Under solvent-free conditions, rapid and efficient synthesis of 1,8-dioxo-decahydroacridine and N -substituted 1,8-dioxo-decahydroacridine derivatives could also be achieved using ammonium acetate and aromatic amines as the nitrogen source.

A series of bis(1,2,4-triazole-3-thiols) 3a–d were prepared by condensation reactions of arylbis(carboxymethylthio)methanes 2a–d with thiocarbohydrazide. The starting diacids 2a–d were prepared by reactions of aromatic aldehydes 1a–d with thioglycolic acid. The structures of these newly synthesized compounds are characterized by elemental analysis, IR, and NMR spectroscopy.

Biginelli condensation of aldehydes, cyclopentanone and urea or thiourea in poly(ethylene)glycol 400, at 45°C in the presence of aluminum chloride as a highly efficient catalyst has been developed. The reaction is very fast, clean and environmentally benign for the synthesis of a vast variety of pyrimidinone derivatives.

A short and efficient route to synthesis of a series of N -dichloroacetyl diazabicyclo derivatives has been developed. The compounds were obtained by cycloaddition of levulinic acid or ester with diamine, followed by acylation with dichloroacetyl chloride. All products were characterized by IR, 1 H NMR, 13 C NMR, MS, and elemental analysis. The single crystal of compound 4c was determined by X-ray crystallographic analysis. All compounds were tested for their herbicide safeners activity of protecting maize from injury with acetochlor.