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Mannich bases (β-aminocarbonyl compounds) are important precursors for the synthesis of numerous natural products and such significant drugs as fluoxetine, atropine, and ranitidine.1,2 In their own...

Objective: The study aims at the derivatization of “Phthalides” and synthesizes 3- arylaminophthalides & 3-indolyl-phthalides compounds, and evaluates their anti-tubercular and antioxidant activities. The study has also intended to employ the in silico methods for the identification of possible drug targets in Mycobacterium and evaluate the binding affinities of synthesized compounds. Methods: This report briefly explains the synthesis of phthalide derivatives using ammonium chloride. The synthesized compounds were characterized using spectral analysis. Resazurin Microtiter Assay (REMA) plate method was used to demonstrate the anti-mycobacterial activity of the synthesized compounds. An in-silico pharmacophore probing approach was used for target identification in Mycobacterium. The structural level interaction between the identified putative drug target and synthesized phthalides was studied using Lamarckian genetic algorithm-based software. Results and Discussion: In the present study, we report an effective, environmentally benign scheme for the synthesis of phthalide derivatives. Compounds 5c and 5d from the current series appear to possess good anti-mycobacterial activity. dCTP: deaminasedUTPase was identified as a putative drug target in Mycobacterium. The docking results clearly showed the interactive involvement of conserved residues of dCTP with the synthesized phthalide compounds. Conclusion: On the eve of evolving anti-TB drug resistance, the data on anti-tubercular and allied activities of the compounds in the present study demonstrates the enormous significance of these newly synthesized derivatives as possible candidate leads in the development of novel anti-tubercular agents. The docking results from the current report provide a structural rationale for the promising anti-tubercular activity demonstrated by 3-arylaminophthalides and 3-indolyl-phthalides compounds.

Temperature controlled chemoselective dehydrogenation and aromatization of tetrahydro-β-carbolines, using molecular I2 and H2O2, in DMSO solvent affords a practical access to a series of corresponding 3,4-dihydro-β-carbolines and β-carbolines respectively. This method has been successfully employed in the short synthesis of Kumujian-C, Eudistomin-U, Norharmane Harmane Harmalan and Isoeudistomin-M.

An efficient protocol for the aromatization of tetrahydrocarbazole is described by using catalytic copper(II) chloride dihydrate in DMSO. This newly established methodology has utilized towards the synthesis of naturally occurring carbazole alkaloids, namely 3-methylcarbazole, 3-formyl carbazole, glycozoline, glycozolicine and clauszoline-K. In addition, the protocol is generalized for the aromatization of N-substituted tetrahydrocarbazole, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline and 1,2,3,4-tetrahydro β-carboline to give the corresponding heteroaromatic compounds from very good to excellent yield. Moreover, this method has been proven to be tolerant to a broad range of functional groups with excellent yields.

A metal-free and greener approach for the one-pot direct iodination and dehydrogenation of dihydrobenzo[a]carbazoles has been developed using periodic acid in polyethylene glycol-400 (PEG-400) under mild condition. This method has been proven to be tolerate to a broad range of functional groups, with good to excellent yields include metal-free inexpensive catalyst, easy work-up, benign reaction condition and high regioselectivity. The solvent has been successfully recycled up to 5 times without any loss of activity in an aqueous medium.

Seventeen (E)-1-(8-hydroxyquinolin-7-yl)-3-phenylprop-2-en-1 one derivatives were synthesized via aldol condensation of substituted benzaldehydes with quinoline chalcones starting from 8-hydroxy quinoline. Molecular docking studies were performed on COX-2 protein for analgesic activity and PDE 4 enzyme for anti-asthmatic activity. Docking studies for analgesic activity reveal that the compounds 2 , 4 , 12 , 14 , and 15 showed significant interaction in terms of hydrogen bonding, hydrophobic attachment and van der Waal interaction with COX-2. The docking studies and pharmacological screening indicate that substitution of hydroxyl and conjugated ketone groups on the aldehyde ring and the quinoline ring accelerates analgesia with better binding to active site. Eddy’s hot plate method was used to evaluate analgesic activity of the synthesized compounds. Compounds showed a substantial increase in reaction time when compared with standard pentazocin. Compounds 2 , 4 , 7 , 9 and 13 showed significant binding interactions with PDE 4 enzyme and hence were selected for evaluation of anti-asthmatic activity using the goat tracheal chain method. Studies reveal that substitution of the methoxy group at 4th & 5th positions for compounds 2 , 4 & 7 leads to significant percentage inhibition of histamine induced contraction. The synthesized compounds are thus found to be potent as analgesic and anti-asthmatic agents.

A convenient route has been developed for mono and dioxygenated carbazole alkaloids from 1-oxotetrahydrocarbazoles. The key step of the synthetic route is the aromatic process of 1-oxotetrahydrocarbazoles using molecular iodine. To our knowledge, this is the first report to manifest a direct synthesis of clausine E, mukonine, mukoeic acid and mukoline, from readily available ester-containing building blocks by using Fischer–Borsche method.

Molecular iodine has been used for the regioselective, one pot, direct synthesis of 3-iodoflavones from 2′-allyloxy chalcones, 2′-hydroxy chalcones and flavones. Allyl deprotection, cyclization dehydrogenation and α-iodination of 2′-allyloxychalcones has been achieved in a single step to offer 3-iodoflavones.

The nanocomposites of TiO2–CeO2 are synthesized by a simple and cost-effective sol–gel method with cetyl trimethyl ammonium bromide (cationic surfactant) as capping agent at 500 °C. The X-ray diffraction analysis revealed phase purity of synthesized product. The X-ray photoelectron spectroscopy showed Ti4+ oxidation state of Ti element while Ce element was exist as a mixture of Ce3+ and Ce4+ oxidation state. The UV–Vis diffuse reflectance spectra clearly indicate the positive alteration in the optical response of TiO2 nanoparticles by the introduction of CeO2 nanoparticles. Scanning electron microscopic study revealed the formation of nanoclusters of spherical particles with uniform size distribution. Energy dispersive X-ray analysis confirmed the elemental composition. Fourier transform infrared spectroscopy analysis confirmed the presence of Ti–O–Ti stretching modes in the range of 900–400 cm−1. Photoluminescence spectroscopy was used to study the rate of recombination and transfer behaviors of photoexcited electron–hole pairs in the nanocomposites. Further, the photocatalytic activity of pure TiO2 nanoparticles and nanocomposite of TiO2 was studied using methyl orange. The TiO2:CeO2 nanocomposites exhibit high dye degradation compare with pure TiO2 nanoparticles. The composite TiO2:CeO2 (7:3) shows highest photocatalytic degradation of methyl orange dye in UV (60 min) and sunlight (90 min).

Substituted phenols were chemo-selectively reacted with benzoylchloride in presence of aluminum chloride under solvent-free condition to afford the corresponding 2'-hydroxy aryl benzophenones in excellent yields (72-96%). Naphthol benzoylation resulted in lower yields as compared to phenols. Both reactions completed in 5-10 min with quantitative yields providing excellent control over regioselectivity of products. KEY WORDS : Chemoselective C-acylation, F-C reaction, Fries rearrangement Bull. Chem. Soc. Ethiop. 2015 , 29(2), 319-325 DOI: http://dx.doi.org/10.4314/bcse.v29i2.14

An efficient regioselective iodination of the Fischer-Borsche ring has been achieved using molecular iodine, in a one-pot synthesis. The acid-, metal-, and oxidant-free conditions of the present method are highly convenient and practical. Furthermore, the one-pot direct iodination process is extended to the concise synthesis of glycozoline, 3-formyl-6-methoxy-carbazole, and 6-methoxy-carbazole-3-methylcarboxylate natural alkaloids. This method has been proven to be tolerant to a broad range of functional groups, with good to excellent yields.

β-Anilinodihydrochalcones readily undergo oxidation α to the carbonyl group region in the presence of a catalytic amount of iodine in dimethyl sulfoxide at 130 °C in good yield. Oxidation of allyloxy-substituted β-anilinodihydrochalcones to β-anilinochalcones is a preferred reaction over deallylation.

A new protocol for the aromatization of tetrahydrocarbazoles has been achieved using a catalytic amount of iodine, giving high yields. The role of iodine in the aromatization has been explained by DFT, and its wide scope is extended to the total synthesis of glycozoline and murrayafoline A. This method has proven to be tolerant of a broad range of functional groups.

The iodine-induced oxidative cyclization of 2′-hydroxychalcones provides a simple, highly efficient approach to various hydroxy flavones and analogues. This process is run under mild conditions, tolerates various functional groups, and provides hydroxy flavones in good to excellent yield. The allyl-protected acetophenones and benzaldehydes were smoothly deallylated under similar conditions.

Azo dyes and nitro-aromatic compounds are the largest group of pollutants released in the environment as industrial wastes. They create serious health and environmental problems. Azoreductases catalyze the reduction of azo dyes and nitro compounds to their respective amines. AN azoreductase was purified up to 12-fold from Lysinibacillus sphaericus using ion-exchange and size exclusion chromatography. It was optimally active at pH 7.4 and 75 °C. It was stable at 70 °C for 30 min. The purified enzyme utilized NADH rather than NADPH as an electron donor to reduce substrates. The molecular weight of the purified enzyme was ~29 kDa. The enzyme also acted as nitroreductase and could selectively reduce the nitro group of 2-nitrophenol, 4-nitrobenzoic acid, 2-nitro-benzaldehyde and 3-nitrophenol. Reduction products of these compounds were identified by IR and NMR.

C-Allyl cleavage has been developed using the inexpensive and mild reagent iodine in dimethylsulfoxide. A variety of compounds with active methylene groups were C-deallylated using this reagent. This method is efficient and operationally simple in comparison to the methods using transition-metal complexes. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

The treatment of 3,3a,4,5-tetrahydro-3-aryl-2-phenyl-2H-benzo[g]indazoles 4 with I2/DMSO led to the oxidation of the five-member rings (5) as well as the iodination of N-phenyl moieties along with oxidation of the five-member rings (6). However, the reactions of 4 with CuCl2/DMSO gave only compounds 5. The reaction of N-bromosuccinimide (NBS) with compounds 4 resulted in fully aromatization along with bromination at C-5 of the indazole rings (7). The indazole six-member rings in compounds 5 and 6 also underwent aromatization along with bromination by using NBS (7 and 8).

A series of 2-phenyl-2,3-dihydrochromon-4-one derivatives (flavanone derivatives) were synthesized by silica gel assisted isomerization of several α-methyl-2′-hydroxy chalcones in 74%–88% yield. These flavanones were further oxidized to 3-methyl flavones by using iodine in dimethyl sulphoxide at 60°C in presence of acid. The newly synthesized derivatives were evaluated for in vitro study against Staphylococcus aureus, Micrococcus luteus and Staphylococcus epidermis.

Selective O-deallylation of dihydropyrazoles has been achieved by use of iodine (10 mol%) in PEG-400 as ecofriendly solvent. Iodine (10 mol%) in dimethyl sulfoxide at 100 °C also afforded O-deallylation with aromatization compatible with highly reactive N-allyl and formyl groups. The function of iodine in the synthesis of substituted pyrazoles under different conditions is described.

A new protocol for the dehydrogenation of dihydropyridazin-3(2H)-one has been carried out by catalytic amount of iodine in dimethyl sulphoxide in good yield with easy workup.

A convenient protocol for the efficient synthesis of 2-arylpyrazolo[4,3-c]coumarins is described. The synthesis route involves molecular iodine catalyzed oxidative cyclization of 1-phenyl-3-(2'-hydroxyaryl)-4-formyl pyrazoles in dimethylsulfoxide. During the lactonisation of 4-formylpyrazoles, we found that iodine was incorporated into the unsubstituted O/P position of the 3-(2'-hydroxyaryl) group. Under similar conditions o -allyloxy derivative of pyrazoles gave same corresponding lactone derivatives by deallylation, lactonisation, and iodination in one step.

Chromium substituted cobalt ferrospinels were prepared by soft citrate gel method. The synthesized material was characterized by various physico-chemical methods. All the samples showed a single-phase cubic structure. Lattice constant varies from 8.389 to 8.323 A. Transmission electron microscopic study indicated the nanostructure of the catalysts while homogenous grain distribution was presented by scanning electron microscopic studies. The catalytic activity of the samples was investigated towards acetylation of phenols. The presence of active centers on the surface of the material was confirmed through pyridine adsorption studies. The surface acidity of the catalyst is responsible for better catalytic performance. The material was found to serve as a promising catalyst for acylation and benzoylation of phenols under solvent free condition. These catalysts are ∼100% selective towards o -acylation of phenols, a promising reaction for perfumery intermediates. The catalysts were seen to be reusable without any further treatment. Catalytic activities of cobalt, chromium and iron oxides were also investigated for comparison. The cobalt ferrospinel was found to have better catalytic activity as compared to the Cr-substituted ferrospinels and the pure oxides. Cobalt ferrite catalyst offers high yields in a short reaction time under solvent-free conditions.

A metal-free protocol for the direct oxidative de-alkoxycarbonylation of alkyl phenyl acetate has been carried out by molecular iodine with good yield. In the present Letter, the vital role of iodine in oxidative de-alkoxycarbonylation is described. This method has been proven to be tolerant to a broad range of functional groups.

Synthesis of flavones from 2'-allyloxy-α, β-dibromochalcones has been described. The iodine induced oxidative cyclization of 2'-allyloxy-α, β-dibromochalcones results into the formation of 3-bromoflavanones which ultimately gives flavones. Dehydrobromination of 3-bromoflavanone to give flavone is the preferred reaction over dehydrogenation. 6 3-Bromoflavones are used in drugs and for synthesis of alkylated and arylated flavones. It is observed that variety of chalcones, flavones and flavanones with bromo substituent exhibits anti-tuberculosis activity. 7 6-Bromoflavone has shown binding affinity to central benzodiazepine receptors and anxiolytic effect in mice. 8 3-Haloflavones are used in the synthesis of biflavonoids. 9 Debromination of 1,2-bis(bromomethyl)arenes by using tetrakis(dimethylamino)ethylene (TDAE) in the presence of olefins and catalytic amount of iodine has been reported. 10 As an extension of previous studies 11 we have been interested in the synthesis of 2'-allyloxy-α, β-dibromochalcones, which leads to the corresponding 3-bromoflavones by using iodine in dimethylsulfoxide reagent. In earlier work 2'-allyloxy chalcones when reacted with DMSO-I 2 reagent, allyl group was smoothly removed followed by cyclization and dehydrogenation to give flavones. We envised that α, β-dibromochalcones expected to eliminate HBr and then dehydrogenation to give 3-bromoflavones. Same study is reported in present work.

The intramolecular cyclization of the esters of salicylaldehyde, O-hydroxyacetophenones, methyl salicylate, and 2′-hydroxy chalcones by potassium hydroxide in pyridine leads to a short and convenient synthesis of 3,4-disubstituted coumarins. Twenty 3-phenyl coumarins were synthesized in 80–90% yields. No other by-product, such as 2-benzylchromone or β-diketones, was observed the reactions. The mild reaction condition involves the removal of more acidic benzylic proton, which leads to a relatively cheap, nontoxic, metal-free method for the synthesis of 3-aryl-4-substituted coumarins.

Nanocrystalline manganese substituted lithium ferrites Li{sub 0.5}Fe{sub 2.5-x}Mn{sub x}O{sub 4} (2.5 =0) were prepared by sol-gel auto-combustion method. X-ray diffraction patterns revealed that as the concentration of manganese increased, the cubic phase changed to tetragonal. Magnetic properties were measured by hysteresis loop tracer technique. All the compositions indicated ferrimagnetic nature. The surface morphology of all the samples was studied by using scanning and transmission electron microscopy. The substitution of manganese ions in the lattice affected the structural as well as magnetic properties of spinels. - Graphical abstract: The synthesized nanoparticles shapes, sizes and size dispersibilities were obtained from the transmission electron microscopy (TEM). The TEM micrographs of synthesized samples revealed that, spherical shape with average particle size 50 nm. Selected area electron diffraction pattern (SAED) suggests the polycrystallinity and also the formation of spinel ferrites.

Ferrospinels of copper, cobalt and iron were prepared by the room temperature co-precipitation route to yield high surface area. The formation of single phase was confirmed by X-ray diffraction. The (3 1 1) peak is found to be most intense. Scanning electron micrographs exhibit increase in grain size with increase in cobalt content, similarly the resistivity is also found to increase with increase in cobalt content and these materials have been effectively utilized as novel heterogeneous catalysts for the oxidation of a variety of activated and non-activated alcohols corresponding carbonyl products.

Spinel-phase nanocrystalline CoCr x Fe 2− x O 4 powders (0.0 ≤ x ≤ 2.0) were synthesized by citrate-gel precursor method. The samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and infra-red spectroscopy (FT-IR). The XRD and selected-area electron diffraction (SAED) patterns indicated that the synthesized nanoparticles have single-phase spinel structure without the presence of any other impurities. The changes in electrical and magnetic properties of different stiochiometric compositions have also been investigated. It is seen that with increase in chromium contents, the measured magnetic hysteresis loops become narrow with decreasing trend in saturation magnetization. Electrical resistivity indicated that all the compounds are semiconducting nature.

A convenient method for deprotection of allyl carboxylic esters has been developed by using the inexpensive and environmentally friendly reagent dimethylsulfoxide–iodine. A variety of carboxylic esters were deprotected to the carboxylic acids. This method is more efficient and operationally simple in comparison to methods using transition metal complexes.

Roots of the plant Inula racemosa are used as folk medicine in east Asia and Europe. Inula racemosa in combination with Commiphora mukul was reported to cure myocardial ischemia. However, systematic investigation of the plant for its specific role in heart diseases has not been conducted so far. In the present study, we have reported the isolation of four major constituents A, B, C and D along with some minor constituents from the plant Inula racemosa. Among the major constituent, constituent Dhas been selected first from spectral data and studied for its cardiac activity on isolated frog heart. The experimental data show that constituent D decreases heart rate and force of contraction at 40 mcg/ml. Actions of Adrenaline are blocked by constituent D and it also acts as an agonist for Propranolol. The studies indicate that constituent D produces a negative ionotropic and negative chronotropic effect on frog's heart. These studies can be utilized as a cardiac marker for exploring the cardiac activity of the plant Inula racemosa.

Acinetobacter junii A8 was able to biotransform nitroaromatic compounds like o -nitroaniline, o -nitrotoluene, m -nitrotoluene, 2,4,6-trinitrotoluene and o -nitrophenol under aerobic condition, within 36 h of incubation. These compounds, which are normally considered to be toxic to microorganisms, caused the induction of drug metabolizing enzymes such as cytochrome P-450, aminopyrine N -demethylase, acetanilide hydroxylase and glutathione S -transferase. These enzymes constitute the bacterial mixed function oxidase system. Induction of this system implies its involvement in biotransformation of these nitro compounds. The biotransformed metabolites were characterized by IR, 1 H NMR and GC–mass spectroscopy. It was observed that o -nitroaniline and m -nitrotoluene were reduced to their respective amines, whereas o -nitrotoluene was oxidized to acid. However, 2,4,6-trinitrotoluene (TNT) and o -nitrophenol were completely mineralized. The metabolites of TNT biotransformation were characterized as 2,6-dinitro-4-nitrosotoluene, 4-amino-2,6-dinitrotoluene and 4-amino-2,6-dinitrobenzoic acid. The result of this study showed that these nitroaromatics induced the mixed function oxidase system, which resulted in the degradation of these compounds.

Acinetobacter junii was found to catalyse the oxidative biotransformation of benzaldehyde, 4-methoxybenzaldehyde, vanillin, 3,4-dimethoxybenzaldehyde, 3-methoxybenzaldehyde and phthalaldehyde within 48 h of incubation. During this process, the activities of drug-metabolizing enzymes, such as cytochrome P-450 and acetanilide hydroxylase were found to be increased significantly. Such an increase in activity indicates their involvement in the biotransformation processes. The purified biotransformed products of each carbonyl compound were characterized by H1 NMR and IR spectroscopy, confirming that oxidation to the corresponding carboxylic acid had occurred.

Kodam et al. reported a 100% decolorization of the sulfonated azo dyes Reactive Red 2, Reactive Red 141, Reactive Orange 4, Reactive Orange 7 and Reactive Violet 5 by an unidentified bacterium, KMK 48. High effectiveness was attained within 36 h of incubation at room temperature and neutral pH. Optimum decolorization took place strictly under aerobic conditions, which is contrary to other well-documented reports. Thus, this microorganism seems to be potentially effective for bioremediation of textile-dyeing industry effluents.

Unfortunately, these methods often require oneor more equivalents of these relatively expensive oxidiz-ing agents. Some of these processes also generate equalamounts of metal waste. Furthermore, oxidation reactionsare usually carried out in halogenated organic solvents,typically chlorinated hydrocarbons, which are environ-mentally undesirable. Therefore, developing green, selec-tive and efficient catalysts for the oxidation of alcohols isof paramount importance for both economic and envi-ronmental reasons.During our investigation on selective oxidation reac-tions we recently developed economical method for theoxidation of acetophenone to benzoic acid by using cop-per chloride in DMSO.

A simple, convenient and efficient method for the preparation of novel functionalized 4-indazolyl- and isoxazolyl-substituted pyrazole derivatives via condensation of 2-acetylcyclohexanone derivatives (III) with hydrazine or hydroxylamine, resp., is given.

The protocol is advantageous with regards to operational simplicity and good functional group tolerance.

A simple and highly efficient method for the preparation of allyloxy- and related hydroxyflavones (18 examples in each case) via iodine-induced cyclization of 2′-hydroxy-4-allyloxychalcones (I) is developed.