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Dehalogenative deuteration reactions are generally performed through metal-mediated processes. This report demonstrates a mild protocol for hydrodehalogenation and dehalogenative deuteration of aryl/heteroaryl halides (39 examples) using a reduced odd alternant hydrocarbon phenalenyl under transition metal-free conditions and has been employed successfully for the incorporation of deuterium in various biologically active compounds. The combined approach of experimental and theoretical studies revealed a single electron transfer-based mechanism.

An efficient route towards a heterogeneous transition metal-free catalytic C-H functionalization using a covalently linked graphene oxide-phenalenyl conjugate is described herein (28 examples, which include a core of some biologically relevant biaryl and hetero-biaryls). It is an environmentally benign, economical and heterogeneous platform, whose catalytic activity can easily be regenerated through a simple washing-drying technique and the catalytic activity can be retained even after 10 cycles.

Open-shell phenalenyl chemistry has widely been explored in the last five decades demonstrating its potential in various applications including molecular switch, spin memory device, molecular battery, cathode material, etc. In this article, we have explored another new direction of open-shell phenalenyl chemistry toward transition metal-free catalytic C-H functionalization process. A phenalenyl ligand, namely, 9-methylamino-phenalen-1-one (4a), promoted chelation-assisted single electron transfer (SET) process, which facilitates the C-H functionalization of unactivated arenes to form the biaryl products. The present methodology offers a diverse substrate scope, which can be operated without employing any dry or inert conditions and under truly transition metal based catalyst like loading yet avoiding any expensive or toxic transition metal. This not only is the first report on the application of phenalenyl chemistry in C-H functionalization process but also provides a low-catalyst loading organocatalytic system (up to 0.5 mol % catalyst loading) as compared to the existing ones (mostly 20-40 mol %), which has taken advantage of long known phenalenyl based radical stability through the presence of its low-lying nonbonding molecular orbital.

Herein we report a transition-metal-free synthetic protocol for heterobiaryls, one of the most important pharmacophores in the modern drug industry, employing a new multidonor phenalenyl (PLY)-based ligand. The current procedure offers a wide substrate scope (24 examples) with a low catalyst loading resulting in an excellent product yield (up to 95%). The reaction mechanism involves a single electron transfer (SET) from a phenalenyl-based radical to generate a reactive heteroaryl radical. To establish the mechanism, we have isolated the catalytically active SET initiator, characterizing by a magnetic study.

A cobalt–N-heterocyclic carbene catalyst, in combination with neopentylmagnesium bromide, was found to promote ortho-C[BOND]H functionalization of 2-arylpyridines with 1,2-diarylaziridines through ring-opening alkylation. The reaction affords 1,1-diarylethanes bearing 2-amino functional groups in moderate to good yields under mild room-temperature conditions.

A new series of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and pyrrolo[1,2-a]phenanthrolines were efficiently built up from an 8-hydroxyquinoline derivative or phenanthroline via 1,3-dipolar cycloaddition reaction involving non-stabilized azomethine ylides, generated in situ from the parent furo[3,2-h]quinoliniums/phenanthroliums, in presence of a copper(II) chloride–phenanthroline catalytic system. The methodology combines general applicability with high yields.

7-Aryl substituted furo[3,2-h]quinoliniums have been synthesised in two steps from 5-chloro-8-hydroxy-7- iodo-quinoline through a tandem Sonogashira alkynylation-cyclization pathway using aryl acetylenes followed by quaternisation reaction with alkyl halides under microwave irradiation. The compounds have been characterized spectroscopically and assessed for their sperm-immobilizing efficacy in vitro by modified Sander–Cramer test. Most of the derivatives showed potent spermicidal effect with minimum effective concentration (MEC) ranging from 125�g/ml – 1mg/ml. The results were further confirmed by double fluoroprobe staining with syber14/PI (Propidium Iodide). The mode of spermicidal action was assessed by (a) Hypo-osmotic swelling tests and (b) Scanning electron microscopy. The compounds have been found to be nontoxic to lactobacillus in 36 hours of culture whereas mild to moderately effective on common vaginal pathogens. Taken together it can be inferred that the water-soluble salts prepared from facile technique are potential candidates for spermicides and could further be utilized for the preparation of vaginal contraceptives.

Fused tricyclic oxazaquinolinium salts were synthesized using Amberlite IRA 402(OH) in water and assessed for their sperm-immobilizing efficacy in vitro by modified Sander–Cramer test followed by double fluoroprobe staining of rat sperm. Out of 11 derivatives 3 showed potent spermicidal effect. The mode of spermicidal action was assessed by (a) Hypoosmotic swelling tests, (b) Lipid peroxidation studies, and (c) scanning electron microscopy. Antimicrobial efficacies of the potent derivatives, assessed by disc diffusion as well as by agar and broth dilution methods using human isolates of bacteria and fungi, revealed their moderate antimicrobial potential. The compounds, found to be nontoxic to rabbit erythrocytes by haemolytic assay, may be exploited as microbicidal spermicides.

A novel class of oxaza-dicyclopenta[a,h]naphthalenes was efficiently constructed from furo[3,2-h]quinoliniums through a 1,3-dipolar cycloaddition reaction employing basic alumina as the solid support. The distinguished features of this methodology encompass high yield, minimal reaction time, operational simplicity and general applicability coupled with structural novelty of the products. The intermediate furo[3,2-h]quinoliniums were easily derived through a two-step methodology, namely a tandem Sonogashira–alkynylation–cyclization, followed by quaternization of the furo[3,2-h]quinoline scaffold.

A basic alumina-supported microwave assisted simple methodology has been developed for the synthesis of aryl-heteroaryl methanes (benzylated quinolones) via transition metal catalyzed cross-coupling reaction of halo substituted polynuclear oxa-aza quinolones with benzyl indium, an organometallic reagent easily derived from commercially available benzyl bromide.

Open-shell phenalenyl chemistry has widely been explored in the last five decades demonstrating its potential in various applications including molecular switch, spin memory device, molecular battery, cathode material, etc. In this article, we have explored another new direction of open-shell phenalenyl chemistry toward transition metal-free catalytic C–H functionalization process. A phenalenyl ligand, namely, 9-methylamino-phenalen-1-one (4a), promoted chelation-assisted single electron transfer (SET) process, which facilitates the C–H functionalization of unactivated arenes to form the biaryl products. The present methodology offers a diverse substrate scope, which can be operated without employing any dry or inert conditions and under truly transition metal based catalyst like loading yet avoiding any expensive or toxic transition metal. This not only is the first report on the application of phenalenyl chemistry in C–H functionalization process but also provides a low-catalyst loading organocatalytic ...

A simple and efficient one-pot three component synthesis of tetrahydropyrrolo[3′,4′:3,4]pyrrolo[2,1- a ]isoquinoline-9,11-dione derivatives has been achieved from variously substituted isoquinolines, 2-bromo acetophenone and N -aryl maleimide derivatives in an aqueous micellar medium. The synthesis represents an environmentally benign alternative to classical methods.

The Heck cross-coupling reaction has been employed for efficient conversion of quinolines to benzoxocinoquinoline through a microwave-assisted palladium-catalyzed intramolecular cyclization in the presence of basic alumina.

Friedel–Crafts reaction of differently substituted anilines with ninhydrin in the presence of molecular iodine at ambient temperature constitutes a facile, cost effective, and regioselective synthesis of a series of 2-mono/2,2-bis-(amino-phenyl)-indane-1,3-dione derivatives. Under identical conditions, use of different substituents in aniline ring led to the formation of different products, emphasizing the pivotal role of the nature and position of the substituents in product formation. In vitro antimicrobial activity evaluation of the synthesized molecules against eight bacterial and four fungal strains revealed that four of them possess duel efficacies (bactericidal as well as fungicidal). The activities are attributed to the disruption of architecture of the microbes as revealed from ultrastructural studies (SEM).

Efficient syntheses of a series of novel bisquinolines have been accomplished from 8-hydroxy quinolines under phase transfer catalyzed conditions using tetrabutylamoniumbromide as phase transfer catalyst. In vitro antibacterial and antifungal study of the synthesized analogues revealed six of them to show significant antibacterial and four to show significant antifungal activity. Among them 3c and 6c show most significant antibacterial activities with minimum inhibitory concentration value 32 μg/mL against four bacterial strains. Ultra structural studies of the microbes treated with 6c demonstrated deformation of cell wall and cell agglomeration. The bisquinolines exhibiting bacteriostatic or fungistatic activity may be developed as newer antimicrobial agents.

Basic alumina supported, solvent-free synthesis of novel oxazocines, medium size heterocycles, has been achieved in excellent yields by tandem C-alkylation followed by intramolecular O-alkylation of hydroxyquinoline/isoquinoline(s) with quinolinium salts under microwave irradiation. The method provides a facile and efficient route for the construction of polynuclear bridge-head oxazocines.

A convenient and inexpensive one step methodology has been developed for the synthesis of linear and angular fused quinazolinones. The protocol, which uses amino heterocycles and o-bromo benzyl/naphthyl bromides as reactants, CuI as catalyst, Cs2CO3 as base, l -proline as ligand, and DMF as solvent, proceeds via nucleophilic aromatic substitution of the N-heteroaromatic cationic intermediate followed by in situ aerial oxidation at the benzylic position to the quinazolinone scaffold.

A number of indolizines and pyrrolo[1,2-a]quinolines/isoquinolines were prepared from phenacyl pyridinium, quinolinium and isoquinolinium salts derived from the reaction of the heterocycles with 2-bromo acetophenone with alkynes and alkenes using amberlite-IRA-402 (OH) ion exchange resin as the base. Antibacterial and antifungal studies were carried out against thirteen bacterial and four fungal strains, which revealed that three derivatives (4a, 4b, 7a) out of fifteen are effective against all the thirteen strains and one derivative, 10, showed dual antibactericidal and antifungal efficacy.

Reductive cyclization of w-(8-quinolyloxy)alkyl esters by zinc in acetic acid is shown to constitute a convenient methodology for the synthesis of oxazino- or oxazepino-fused tetrahydroquinolines. It is operationally simple, requires a short reaction time, and provides excellent yields.

Basic alumina supported solvent-free one-pot synthesis of pyridine-fused polycyclic diazepaniums was achieved under microwave irradiation. The process was successfully extended to the synthesis of pyridine-fused bicyclic imidazolidiniums and tetrahydro-pyrimidiniums and also of tri- and tetracyclic diaza-heterocycle-fused quinoliniums. The dual characteristic of basic alumina, a solid support as well as a base, was successfully employed in the current investigation. The method emerged to be an effective route in terms of product yield, reaction time, and ease of purification and most importantly for environment friendly protocols.

A high yielding environmentally benign protocol has been developed for the synthesis of pyrrolo[2,1-a]isoquinoline using chromone-3-carboxaldehyde, isoquinoline and phenacyl bromide/bromoacetic acid ester as reagents in aqueous micellar medium. The method is operationally simple and more effective compared to the previous methods in terms of the yield of the products as well as the reaction time.

Au electrode modified with the self-assembled monolayer of a heterocyclic thiol, mercaptotriazole (MTz), is used for the electroanalysis of uric acid (UA) and ascorbic acid (AA). MTz forms a less compact self-assembly on Au electrode. The self-assembly of MTz on Au electrode favors the oxidation of UA and AA at less positive potential. Significant decrease (∼400 mV) in the overpotential and enhancement in the peak current for the oxidation of interfering AA with respect to the unmodified electrode is observed. The negative shift in the oxidation peak potential of AA favors electrochemical sensing of UA without any interference. Two well-separated voltammetric peaks for AA and UA are observed in their coexistence. The large separation between the two voltammetric peaks allows the simultaneous or selective sensing of the analytes without compromising the sensitivity. Linear response is obtained for a wide concentration range. This electrode could sense as low as 1 μM of UA in the presence of 10-fold excess of interfering AA. No change in the sensitivity (0.012 μA/μM) of the electrode toward UA in the presence and absence of AA is observed. Reproducible and stable amperometric flow injection response was obtained upon repetitive injection.

The efficient syntheses of 6,6,8,6,6-pentacyclic naphtho- fused oxazocinoquinolinones and 6,6,8,6,6,6-hexacyclic ben- zo(g)quinoxalino-fused oxazocinoquinolinones were achieved in one-pot sequences. The generation of libraries of their diaryl- and alkynyl-substituted analogues via Suzuki-Miyaura and Sonogash- ira cross-coupling reactions, respectively, were also achieved.

An environmentally benign protocol has been described for the synthesis of novel 2-(1′,3′-dihydro-1H-[2,3′]biindolyl-2′-ylidene)-indan-1,3-diones/bis-indolylindane-1,3-diones from ninhydrin and 3-substituted/unsubstituted indoles. It uses montmorillonite K-10 as catalyst in a solvent-free condition under microwave irradiation. The method was also used for the synthesis of novel bisindolylindeno[1,2-b]quinoxaline derivatives.

A high yielding green protocol for the synthesis of tricyclic oxaza quinolinium salts has been developed using Amberlite IRA 402(OH) in water. This method is more effective compared to previously reported phase-transfer catalytic (PTC) condition in terms of yield of the product, reaction time and ease of separation.

A facile synthesis of novel di-spiro compounds has been achieved via 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin derivatives and sarcosine to the conjugated double bond of andrographolide. When the amino acid was changed from sarcosine to l-proline, the product formation took a different course as determined by 2D NMR and X-ray crystallographic analysis.

A high yielding green protocol has been developed for the synthesis of tri-, tetra-, and pentacyclic fused 2-quinolones in micellar medium. The method is more effective compared to phase-transfer catalytic (PTC) method in terms of the yield of the product as well as the reaction time. It is operationally simple as well as environmentally benign.

Acetylenic 8-quinolinols generated in situ by the Sonogashira cross-coupling reaction are efficiently converted into furo[3,2-h]quinolines by microwave-assisted, copper-catalyzed, intramolecular cyclization in the presence of basic alumina.

Amberlite IRA 402(OH) effectively mediates biarylation via Suzuki-Miyaura cross-coupling reaction on complex systems such as dihalo quinolonoquinoxalino-oxazocines.

An efficient and simple synthesis of pentacyclic quinolonoquinoxalinooxazocines in a one-pot sequence has been performed by unique application of phase transfer catalysis. Preparative simplicity and conceptual novelty of the methodology offer an attractive general application for the synthesis of novel quinoline antibiotics.

Syntheses of 3,3-diheteroaromatic oxindole derivatives has been achieved by coupling indole-2,3-dione (isatin) with differently substituted indoles and pyrrole in presence of I(2) in i-PrOH. The in vitro spermicidal potentials and the mode of spermicidal action of the synthesized analogues were evaluated and the derivative, 3,3-bis (5-methoxy-1H-indol-3-yl) indolin-2-one (3d) exhibited most significant activity.

A general and highly efficient synthetic protocol under phase transfer catalytic condition has been established for the synthesis of fused tetracyclic oxazocinoquinolone analogues which served as the precursors for novel biaryl quinolones using microwave assisted Suzuki cross coupling reaction.

A high yielding green protocol is described for the synthesis of 3,2 and 3,3-diheteroaromatic oxindole involving the condensation of isatin with indole or pyrrole in an aqueous medium under neutral conditions by supramoleculer catalysis by β-cyclodextrin. The β-cyclodextrin can be easily recovered and reused without any loss of activity.

Ortho-C–H benzylation of aryl ketimines with benzyl phosphates is achieved with the aid of a catalytic system consisting of a cobalt(II) salt, a phosphine/pyridine bidentate ligand, and a Grignard reagent under room-temperature conditions, affording a variety of diarylmethanes bearing o-acetyl or -acyl groups in moderate to good yields. Owing to the versatility of the o-acetyl group, the reaction opens useful synthetic routes to polycyclic compounds such as unsymmetrical anthracene, anthracenone, and anthraquinone derivatives.

Ortho-C–H benzylation of aryl ketimines with benzyl phosphates is achieved with the aid of a catalytic system consisting of a cobalt(II) salt, a phosphine/pyridine bidentate ligand, and a Grignard reagent under room-temperature conditions, affording a variety of diarylmethanes bearing o-acetyl or -acyl groups in moderate to good yields. Owing to the versatility of the o-acetyl group, the reaction opens useful synthetic routes to polycyclic compounds such as unsymmetrical anthracene, anthracenone, and anthraquinone derivatives. MOE (Min. of Education, S’pore) Accepted version

2-Arylpyridines with substituent at the ortho-position of the benzene ring or the 3-position of the pyridine ring only afford trace amounts of the desired products.

The preparation of the target system (V), which is required for DNA studies, involves initial deprotonation of substrates (III) by basic alumina, trapping of the resulting 1,3-dipole with acetylenic esters and subsequent aromatization.

A facile synthesis of the title compounds (16 examples) is completed by 1,3-dipolar cycloaddition of isoquinolinium ylides to phenyl maleimide derivatives.

Dispiro-pyrrolidino/pyrrolizidino fused oxindoles/acenaphthoquinones have been derived from andrographolide via azomethine ylide cycloaddition to the conjugated double-bond under microwave (MW) irradiation. The reactions are chemo-, stereo-, and regioselective in nature. Change in amino acid from sarcosine/N-benzyl glycine to l-proline changes the regiochemistry. A representative library of 40 compounds along with in vitro anticancer evaluation is reported.

Background An alarming increase in global population is the root cause of poverty, malnutrition, sexually transmitted infections (STIs) and many other social problems. Microbicidal spermicides possessing dual function of contraception and STI protection can effectively combat this problem, and their development is of utmost importance at present. Study Design A major metabolite isolated from Shorea robusta resin was spectroscopically characterized as asiatic acid. Spermicidal efficacy of the isolate was evaluated in vitro by a modified Sander–Cramer test. The mode of spermicidal action was assessed by (a) double fluoroprobe staining, (b) hypoosmotic swelling test and (c) scanning electron microscopy. Antimicrobial efficacy was assessed by disc diffusion and broth dilution methods using human isolates of bacteria ( Escherichia coli ATCC 25938 and Pseudomonas aeruginosa 71) and fungus ( Candida tropicalis ). Results The minimum effective concentration of asiatic acid that induced instantaneous immobilization of rat spermatozoa in vitro was 125 mcg/mL. The mechanism of action involved disruption of sperm plasma membrane. The microbicidal efficacy was found to be moderate for vaginal pathogens, with no effect on normal vaginal flora. Conclusion Asiatic acid possesses appreciable spermicidal and microbicidal potential and may be explored as an effective microbicidal spermicide.

Basic alumina supported, solvent-free synthesis of novel oxazocines, medium size heterocycles, has been achieved in excellent yields by tandem C-alkylation followed by intramolecular O-alkylation of hydroxyquinoline/isoquinoline(s) with quinolinium salts under microwave irradiation. The method provides a facile and efficient route for the construction of polynuclear bridge-head oxazocines.

Treatment of esters (I) and (III) with zinc in acetic acid allows formation of title compounds (II) and (IV) under environmentally friendly mild conditions.

A two-step one-pot protocol is developed for the synthesis of a series of title compounds including different benzofused analogues.

A phase transfer promoted synthesis of halogen-substituted title compounds such as (III) and (VIII) is described and their utility in Pd-catalyzed coupling reactions is demonstrated.

The improved protocol for the preparation of the biologically interesting title compounds uses the Amberlite resin instead of phase transfer catalysts.

A high yielding green protocol has been developed for the synthesis of tri-, tetra-, and pentacyclic fused 2-quinolones in micellar medium. The method is more effective compared to phase-transfer catalytic (PTC) method in terms of the yield of the product as well as the reaction time. It is operationally simple as well as environmentally benign.

Amberlite IRA 402(OH) effectively mediates biarylation via Suzuki-Miyaura cross-coupling reaction on complex systems such as dihalo quinolonoquinoxalino-oxazocines.

Basic alumina used in lieu of traditional mineral bases efficiently promotes a solvent free, Pd(PPh3)4 catalyzed Suzuki–Miyaura cross-coupling reaction under microwave irradiation.