DMSO promoted catalyst-free oxidative C-N/C-O couplings towards synthesis of imidazoles and oxazoles.

Dimethyl sulfoxide (DMSO)-promoted catalyst-free oxidative C-N coupling and C-O coupling under oxidant-free conditions are outlined. This protocol is operationally simple and leads to various functionalized substituted imidazoles or oxazoles in good yields. To date, a very limited number of oxidation protocols have been established, where DMSO acts solely as a catalyst or an oxidant or both. In this report, DMSO is not only used as a C-N/C-O coupling agent but is also used as the oxidant required for these oxidative transformations. Hence, our demonstrated DMSO-promoted catalyst-free coupling transformation has the ability to lead to a new dimension in the field of oxidative coupling.

Substrate Switchable Pathway for Selective Construction of Bridged Dibenzo[b,f][1,5]diazocines and Bridged Spiromethanodibenzo[b,e]azepines.

An operationally simple method for the synthesis of bridged dibenzo[b,f][1,5]diazocines and bridged spiromethanodibenzo[b,e]azepines exhibiting bridged eight-membered and seven-membered molecular architecture is reported. This unique approach is based on substrate selective mechanistic pathway, including an unprecendented aerial oxidation-driven mechanism for the synthesis of bridged spiromethanodibenzo[b,e]azepines. The reaction is highly atom economic, and in addition, it allows the construction of two rings and four bonds in a single operation under metal-free condition. The easy availability of ß enaminone and ortho phathalaldehyde as starting materials and the simple operation make this approach suitable for the preparation of important dibenzo[b,f][1,5]diazocine and spiromethanodibenzo[b,e]azepine cores.

Aqueous mediated iodine catalyzed C-N coupling followed by C-C coupling towards 5H-pyrazino[2,3-b]indoles.

Our study describes a new development featuring iodine-catalyzed two consecutive oxidative cross-coupling reactions involving Cα(sp3)-H of benzyl amines followed by intramolecular cyclization in water under air. Here, C-N coupling followed by C-C coupling occurs in a green environment to provide a variety of 5H-pyrazino[2,3-b]indoles within a short time period.

Steric-Hindrance-Induced Diastereoselective Radical Nitration of 3-Alkylidene-2-oxindoles Followed by Tosylhydrazine-Mediated Sulfonation.

Metal-free radical nitration of the ß C-H bond of 3-alkylidene-2-oxindoles with tert-butyl nitrite (TBN) has been explored. Interestingly, (E)-3-(2-(aryl)-2-oxoethylidene)oxindole and (E)-3-ylidene oxindole give different diastereomers on nitration. The mechanistic investigation revealed that the diastereoselectivity was controlled by the size of the functional group. Another transformation of 3-(nitroalkylidene) oxindole into 3-(tosylalkylidene) oxindole was performed through metal and oxidant-free tosylhydrazine-mediated sulfonation. Both methods have the advantages of readily available starting materials and operational simplicity.

Metal-free, I2-promoted direct synthesis of 2-cyano-substituted maleimides via a unique 3,3-dicyano-2-arylacrylic acid intermediate.

A robust, I2-mediated cyclization reaction was developed for the synthesis of 2-cyano-substituted maleimides from arylethylidene malononitriles and amines via unique a 3,3-dicyano-2-arylacrylic acid intermediate. The reaction duration was short and devoid of an expensive transition-metal catalyst, ligands or toxic carbon monoxide. We executed an I2/DMSO-mediated desirable oxidation of the C(sp3)-H bond of the carbonyl precursor followed by the formation of a 3,3-dicyano-2-arylacrylic acid intermediate. Use of readily available starting materials under mild and operationally simple reaction conditions are the major advantages of this strategy.

Diastereo- and regioselective petasis aryl and allyl boration of ninhydrins towards synthesis of functionalized indene-diones and dihydrobenzoindeno-oxazin-ones.

Petasis aryl and allyl borations were accomplished using substituted ninhydrins, boronic acids or 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane and 1,2-aminophenols in Hexafluoroisopropanol (HFIP) without any catalysts to synthesize different aryl and allyl derivatives of ninhydrins. The nature of substitution in the boronic acids and 1,2-amino phenols was the key factor in determining the diastereo-regioselectivity and the type of product distributions. The products were isolated and characterized by HMBC, HSQC, 1H, 13C NMR experiments and X-ray single crystallographic analysis. A probable reaction pathway involves in situ formation of acyclic and cyclic ninhydrin-amino alcohol adducts, with the positioned hydroxyl group determining the stereo-regioselective outcome via tetracoordinated boron intermediates. A metal free diastereo- and regioselective Petasis aryl and allyl boration of ninhydrins.

FeCl3-Catalyzed Synthesis of 6-Thioxo-hexahydroindeno[1',2':4,5]imidazo[1,5-a]pyridin-12(6H)-ones via an Interesting [1,2] Oxygen Shift Pathway.

An iron-catalyst mediated one-pot multicomponent route for the synthesis of novel 6-thioxo-hexahydroindeno[1',2':4,5]imidazo[1,5-a]pyridin-12(6H)-one scaffolds has been developed using ninhydrin, l-proline, and aryl isothiocyanates in ethanol medium. This methodology offers an interesting [1,2] oxygen shift mechanism pathway via a number of ring-opening and ring-closing cascade steps to provide diverse substituted hexahydroindeno-imidazo[1,5-a]pyridinones in excellent to good yields. The stereochemistry of the proline ring is lost during the course of the reaction. This protocol is well acceptable toward both electron-accepting and electron-donating functionalities at the ortho-, meta-, and para-positions of the isothiocyanate moiety. Nonhazardous conditions, step economic, and easy operational process are the advantages of this methodology.

Tosylhydrazine-promoted self-conjugate reduction-Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives.

An efficient tosylhydrazine-mediated conjugate reduction of 3-phenacylideneoxindole and sequential Michael/intramolecular aldol reaction is reported under base-catalyzed conditions towards the formation of densely substituted dispirocyclopentanebisoxindole derivatives. The reaction proceeded in a diastereoselective manner to afford four chiral stereocenters. The method also has advantages of wide substrate scope, readily available starting materials and operational simplicity through one pot reaction.

Green synthesis of C5-C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni-chitosan nanocatalyst under ultrasonic conditions.

A heterogeneous and magnetically recyclable Ni-chitosan nanocatalyst was synthesized and thoroughly characterized by powder Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray (EDX) spectroscopy, etc. It was effectively utilized in the eco-friendly synthesis of new C5-C6-unsubstituted 1,4-DHPs under ultrasonic irradiation. The important focus of the methodology was to develop an environmentally friendly protocol with a short reaction time and a simple reaction procedure. The other advantages of this protocol are a wide substrate scope, a very good product yield, the use of an eco-friendly solvent and a recyclable nanocatalyst, as well as reaction at room temperature.

An environment-friendly methodology for the construction of diversified bicycloacenaphtho[1,2-d]imidazole-8-thione scaffolds using spinel NiFe2O4 nanoparticles as a sustainable catalyst.

Herein, we successfully developed an easy access to bicycloacenaphtho[1,2-d]imidazole-8-thione by one-pot three-component MCRs of acenaphthoquinone, aryl or alkyl isothiocyanates and amines using environmentally benevolent and recyclable spinel NiFe2O4 nanocatalyst in aqueous ethanol. A broad number of products have been synthesized with both EDGs and EWGs present in the ring which increases the diversity of the protocol. The NiFe2O4 nanopowder has been synthesized and thoroughly characterized by powdered XRD, HRTEM, EDX, BET and ICP-AES analysis. The protocol to this bicyclic-heterocycle is noteworthy due to good to excellent yields, practical simplicity and high regioselectivity without any troublesome or hazardous by-products and its easy recovery and reusability of the catalyst. Spinel NiFe2O4 NPs-catalysed synthesis of various bicycloacenaphtho[1,2-d]imidazole-8-thione scaffolds under mild and sustainable conditions.

A quick accelerating microwave-assisted sustainable technique: permutated spiro-casing for imaging experiment.

A quick access tool for the one-pot, chromatography-free synthesis of the diversified dihydrospiro[indeno[1,2-b]pyridine-4,3'-indoline or acenaphthylene-1,4'-indeno[1,2-b]pyridine spiro-analogous via sustainable microwave condition in minimal 1:1 (v/v) aqueous ethanol without any metal catalyst is demonstrated here. This permutated spiro-casing was designed as fluorescence probe at physiological pH for selective detection of Zn2+, even in the presence of other competitive ions and showed a fluorescent enhancement with 1:1 metal/ligand complex. Moreover, this spiro sensor was successfully applied as an effective intracellular Zn2+ imaging agent in the biomedical study of human hepatocellular liver carcinoma cells (HepG2) due to its cell permeability property. A quick access technique for the permutated dihydrospiro-pyridine via chromatography-free sustainable microwave condition and its applications as organic fluorescence probe at physiological pH for selective detection of Zn2+ and effective intracellular Zn2+ imaging in HepG2 cells.

Pseudo five component reaction towards densely functionalized spiro[indole-3,2'-pyrrole] by picric acid, an efficient syn-diastereoselective catalyst: insight into the diastereoselection on C(sp3)-C(sp3) axial conformation.

A new series of highly-functionalized spiro compounds of pyrrole were synthesized by a one pot, step-economic condensation of isatin, arylamine and ß-keto ester catalyzed by wet picric acid. Initially, the reaction was proposed with an expectation of the formation of a multi-spiro heterocyclic framework of highly-substituted piperidine. However, the isomeric compound was characterized to be a five-membered pyrrole derivative with a diverse scope of variations having different types of substituents in the three components respectively. The possibility of formation of various diastereomers around the hindered single bond and the spiro carbon was limited, as only syn products syn-60 and syn-60' were isolated in all the reactions performed under the standard conditions. Probably the reactions were mediated by the si-facial formation of the bonds in a picric acid stabilized charge transfer complex transition state. Also, the manner a molecule achieves the most stabilized energy minimized arrangement with all its substituents in space was studied by DFT calculations where syn-60 was more stable than syn-60'. The studies on the formation of syn-60 and syn-60' were carried out by variation of electronic and steric factors in each of the components of the reactions.

Dihydroindeno[1,2-b]pyrroles: new Al3+ selective off-on chemosensors for bio-imaging in living HepG2 cells.

In this study, a new molecular organic probe has been designed and synthesized by using recyclable, inexpensive and non-toxic polyethylene glycol (PEG-400) as a promoting reaction medium in water under environmentally benevolent conditions. The probe has been explored as a potential chemosensor to detect Al3+ ions using a HEPES buffer (pH = 7.4) solution. Investigations of the fluorescence behaviour of this sensor in DMSO/H2O (2 : 8, v/v) solution displayed a dramatic switch-on response only in the presence of Al3+, while other metal ions, like Li+, Na+, K+, Ag+, Ca2+, Mg2+, Mn2+, Ba2+, Cu2+, Ni2+, Co2+, Fe2+, Zn2+, Cd2+, Hg2+, Pb2+, Sr2+, Fe3+ or Cr3+, have almost no influence on the fluorescence behaviour. Various common anions, such as ClO4-, Cl-, or NO3- in the form of Al3+ salts [e.g. Al(ClO4)3, AlCl3 or Al(NO3)3], had no influence on the fluorescence behaviour of the sensors. The detection limit for Al3+ is in the order of 10-6 M in DMSO/H2O (2 : 8, v/v) HEPES buffer (pH = 7.4) solution. Notably, this is the first report of a dihydroindeno[1,2-b]pyrrole moiety acting as a sensor for the selective detection of Al3+ ions through an off-on fluorescence response. The potential of the probe was also confirmed by employing it for fluorescence bio-imaging with Al3+ on HepG2 cells.

I2 catalyzed access of spiro[indoline-3,4'-pyridine] appended amine dyad: new ON-OFF chemosensors for Cu2+ and imaging in living cells.

An easy access to an amine-appended spiro[indoline-3,4'-pyridine] ON-OFF chemosensor by a one-pot four-component reaction using commercially available and an environmentally benign catalytic amount of molecular I2 (10 mol%) in aqueous ethanol at ambient temperature is described. The generated system could be utilized for the selective detection of Cu2+ as it demonstrated a colorimetric naked eye change along with an ON-OFF fluorescence response towards Cu2+ at physiological pH. The sensors exhibited high selectivity for Cu2+ over other common cations with detection limit in the range of 10-7 (M). Notably, this is the first report of a spiro[indoline-3,4'-pyridine] moiety acting as a sensor for Cu2+via a on-off fluorescence response. In addition, the probe system was successfully applied for imaging Cu2+ in human hepatocellular liver carcinoma cells (HepG2), demonstrating a new avenue for molecular imaging and biomedical applications.

Recognition of steric factor in external association of xanthenocrown-5 and bis-napthalenocrown-6 with bis(benzimidazolium)propane borontetrafluoride.

This is the first report of charge transfer band for crown-axel H-bonding interaction in acetonitrile medium. Monte Carlo simulation established external association of small cavity crown with BBIM-propane dication axels. Resonance energy, binding constant and ratiometric detection of association of xanthenocrown-5 (1) and bis-napthalenocrown-6 (2) with bis-(benzimidazolium)propane borontetrafluoride (3a-3d) in acetonitrile determined the effect of steric factor towards association.

Cross-dehydrogenative regioselective Csp³-Csp² coupling of enamino-ketones followed by rearrangement: an amazing formation route to acridine-1,8-dione derivatives.

A new general method for the synthesis of acridine-1,8-diones through CDC coupling of enamino-ketones followed by rearrangement has been developed. This is a Cu(i) catalyzed procedure, based on the cross dehydrogenative coupling of the Csp(3)-H bond with the Csp(2)-H bond of enamino-ketones followed by rearrangement to acridine-1,8-diones in the presence of PTSA under an aerobic atmosphere. The synthetic route has been broadly applicable to a wide range of enamino-ketone derivatives derived from different benzyl amines as well as primary aliphatic amines having Cα(sp(3))-H bonds with various cyclic, acyclic 1,3-diketones and also using DEAD.

Synthesis and photophysics of selective functionalized π-conjugated, blue light emitting, highly fluorescent C7-imidazo indolizine derivatives.

A new family of novel highly fluorescent π-conjugated, C7-imidazole based indolizine derivatives has been prepared in good to excellent yields, catalysed by l-proline in acetonitrile. These are π-conjugated, C7-imidazole based indolizine derivatives covering the emission wavelength range 423-449 nm in acetonitrile with high quantum yields at 25 °C. A thorough photophysical study of all the compounds has been carried out to understand the π-conjugated electronic effect of the imidazole moiety fused at the C7 position on the indolizine motif. In addition, a comparative photophysical study of three selective fluorophores was also carried out in a wide variety of solvents at 25 °C. Finally, the molecular orbitals of the two representative compounds were investigated through DFT calculations to illustrate the pi-conjugate effect.

FeCl3-Catalyzed Combinatorial Synthesis of Functionalized Spiro[Indolo-3,10'-indeno [1,2-b]quinolin]-trione Derivatives.

An efficient, inexpensive, environmentally friendly and high yield one-pot route to new spiro[indolo-3,10'-indeno [1,2-b]quinolin]-trione derivatives has been developed, involving three-component reaction of enaminones, N-substituted isatins and Indane-1,3-dione catalyzed by FeCl3. The approach to this spiro-heterocycle is noteworthy because it results in the formation of three new σ (two C-C and one C-N) bonds in a single operation, leading to the construction of novel spiro skeleton. This method works on a large scale in excellent yields.

Simultaneous sonication assistance for the synthesis of pyrroloacridinones and its efficient catalyst HBF4 supported on uniform spherical silica nanoparticles.

Fluoroboric acid (HBF4) adsorbed on mesoporous silica nanoparticles of 600nm dimension was synthesized and characterized by N2 adsorption, HRTEM, EDX, XPS. The applicability of silica-HBF4 was probed through the sonication assisted synthesis of pyrroloacridinones in ecofriendly solvent ethanol. Standard leaching experiment was performed to show that the reaction was heterogeneous with this recyclable catalyst.

Cubic Perovskite ZnTiO3 Nanopowder as a Recyclable Heterogeneous Catalyst for the Synthesis of 1,6-Naphthyridines in Water.

Cubic perovskite ZnTiO3 nanopowder has been prepared by means of a sustainable sol-gel method. The nanopowder (12-20 nm) has been thoroughly characterized by N2 sorption analysis, high-resolution (HR) TEM, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), SEM, and FTIR analyses. The environmentally benign synthesis of highly substituted 1,6-naphthyridines catalyzed by ZnTiO3 nanopowder in aqueous media has been demonstrated. It requires two different catalytic functions, that is, an acid one, which is provided by TiIV ions, and a basic one, which is provided by the oxide ion incorporated within the ZnTiO3 metal oxide framework. 1,6-Naphthyridines are of tremendous biological importance, and this method is simple and environmentally friendly. The greenness of the process was satisfactorily established as water was exploited as the reaction medium and there was very high atom economy.