Neat Conditions Research Articles

Combined Experimental and Computational Study on Catalytic Cyclocoupling of Epoxides and CO2 Using Porphyrin-Based Cu(II) Metal-Organic Frameworks with 2D Coordination Networks

Abstract The cyclocoupling of epoxides and CO2 was investigated using porphyrin-based Cu(II) metal-organic frameworks with 2D coordination networks. A variety of mono- and disubstituted epoxides were transformed into cyclic carbonates under mild and neat conditions. Several control experiments were carried out to elucidate that the catalytically active site is the dicopper paddle wheel unit rather than the copper porphyrin complex moiety. The proposed mechanism was corroborated by density functional theory calculations of a model paddle wheel unit.

Development and optimization of a new synthetic process for lorcaserin

A two-step process to synthesize racemic lorcaserin was developed from 2-(4-chlorophenyl)ethanol via formation of bromide or tosylate derivatives. These derivatives were reacted with allylamine in neat conditions to provide pure N-(4-chlorophenethyl)allylammonium chloride. This compound was cyclized in neat conditions using aluminum or zinc chloride to give racemic lorcaserin. After resolution of enantiomers, the wrong enantiomer was racemized and recycled to give new R-lorcaserin.

Solvent‐free, l‐Leucine‐Catalyzed Direct Dehydrative Esterification of Carboxylic Acids with Alcohols: Direct Synthesis of 3‐Alkoxy 1(3 H)‐isobenzofuranone

AbstractA l‐leucine‐catalyzed mild and efficient method has been developed for the synthesis of open‐chain as well as cyclic esters. A wide range of alcohols, including primary, secondary, and tertiary with aliphatic and aromatic side chains, were successfully tolerated. In the case of 2‐carboxybenzaldehydes with different alcohols, 3‐alkoxy‐1‐(3 H)‐isobenzofuranones were obtained in good yields. Alcohols from natural origin have also been reacted with various acids successfully to get the corresponding esters. The reaction proceeded under neat conditions and there is no need for any acid, base, or removal of water during the reaction.

An improved solvent-free synthesis of flunixin and 2-(arylamino) nicotinic acid derivatives using boric acid as catalyst

A simple solvent-free protocol for the preparation of flunixin, a potent non-narcotic, non-steroidal anti-inflammatory drugs is reported using boric acid as catalyst. Its salt, flunixin meglumine are then prepared under reflux in EtOH. This sustainable method are then extended for the synthesis of a series of 2-(arylamino) nicotinic acid derivatives. The present protocol combines non-hazardous neat conditions with associated benefits like excellent yield, straightforward workup, and use of readily available and safe catalyst in the absence of any solvent, which are important factors in the pharmaceutical industry. The pathway for catalytic activation of 2-chloronicotic acid with boric acid was also investigated using Gaussian 03 program package.

Magnetically recoverable AlFe/Te nanocomposite as a new catalyst for the facile esterification reaction under neat conditions

In this work, a new Fe3O4/AlFe/Te nanocomposite was synthesized by a one‐step sol–gel method. The Fe3O4 magnetic nanoparticles (MNPs) were prepared and then mixed with aluminum telluride (Al2Te3) in an alkali medium to produce the desired catalyst. After characterization of the Fe3O4/AlFe/Te nanocomposite by SEM, TEM, EDS, XRD, and ICP analyses, it was used in the esterification reaction. This heterogeneous catalyst showed high catalytic activity in the esterification of commercially available carboxylic acids with various alcohols to produce the desired esters at high conversions under neat conditions. The Fe3O4/AlFe/Te nanocomposites were separated from the reaction mixture via an external magnet and re‐used 8 times without significant loss of catalytic activity.

Palladium(II) acetate catalyzed acylative cleavage of cyclic and acyclic ethers under neat conditions

During the development of a palladium catalyzed C–H activation cross-coupling reaction involving acyl halides, it was noted that palladium(II) acetate catalyzes the acylative cleavage of tetrahydrofuran (used as a solvent) at room temperature to afford the corresponding 4-chlorobutyl ester derivative. After optimization, the reaction was shown to work well with epoxides, oxetane and tetrahydrofuran, but only barely with oxanes at room temperature. Acyclic ethers systematically failed to react under similar conditions, but underwent complete conversion in a microwave reactor at 100 °C.

An efficient catalytic method for the synthesis of pyrido[2,3‐d]pyrimidines as biologically drug candidates by using novel magnetic nanoparticles as a reusable catalyst

A convenient method for the synthesis of pyrido[2,3‐d]pyrimidines by using the novel nano‐magnetic silica‐bonded S‐sulfonic acid[Fe3O4@SiO2@(CH2)3S–SO3H] as an efficient and recyclable catalyst under neat conditions is described. The major advantages of the present methodology are high yield, short reaction time, and reusability of the catalyst. Furthermore, the nano‐magnetic silica‐bonded S‐sulfonic acid was fully characterized by using various techniques such as FT‐IR, TG/DTG, DTA, EDX, μXRF, XRD, HRTEM, SEM, SEM elemental mapping, XPS, and N2 physisorption. The results obtained from this research support the idea of rational design, synthesis, and applications of task‐specific and reusable catalysts for the preparation of various polynitrogenated heterocyclic compounds containing 1,4‐dihydropyridine moieties.

Solvent-Free Addition of Indole to Aldehydes: Unexpected Synthesis of Novel 1-[1-(1H-Indol-3-yl) Alkyl]-1H-Indoles and Preliminary Evaluation of Their Cytotoxicity in Hepatocarcinoma Cells.

New 1-[1-(1H-indol-3-yl) alkyl]-1H-indoles, surprisingly, have been obtained from the addition of indole to a variety of aldehydes under neat conditions. CaO, present in excess, was fundamental for carrying out the reaction with paraformaldehyde. Under the same reaction conditions, aromatic and heteroaromatic aldehydes afforded only classical bis (indolyl) aryl indoles. In this paper, the role of CaO, together with the regiochemistry and the mechanism of the reaction, are discussed in detail. The effect of some selected 3,3′- and 1,3′-diindolyl methane derivatives on cell proliferation of the hepatoma cell line FaO was also evaluated.

Malachite Green Derivatives for Dye-Sensitized Solar Cells: Optoelectronic Characterizations and Persistence on TiO2

Abstract Derivatives of malachite green, a well-known triphenylmethine dye, have been adapted for third-generation photovoltaic applications as dye-sensitized solar cells (DSSC). The solar cells were developed based on a concentrated Br3−/Br− liquid electrolyte coupled to different trifluoroacetate (TFA−), triflate (TfO−), bromide (Br−) and tetrafluoroborate (BF4−) malachite green salts as dye sensitizers and mesoporous TiO2 anatase as electron collector, and their optoelectronic properties were characterized. The adsorption patterns of such salts at the TiO2 nanoparticle surface were studied by zeta (ζ) potential measurements on colloidal suspensions under neat conditions, and compared to the desorption rates of the dyes when exposed to the DSSC electrolyte. The different affinities of the ionic pairs for the oxide surface and the bulk were found crucial for the stability of the self-assembled monolayer of carboxylic acid-anchored chromophores at the surface, and for the photoconversion efficiency associated therewith. This study aimed at depicting the behavior of the ionic pairs at the surface and gave insights for their physical and chemical stabilization in the DSSC environment.

Metal- and Solvent-Free Approach to Diversely Substituted Picolinates via Domino Reaction of Cyclic Sulfamidate Imines with β,γ-Unsaturated α-Ketocarbonyls

An efficient, solvent-free, and eco-friendly domino reaction of 5/6-membered cyclic sulfamidate imines with a variety of β,γ-unsaturated α-ketocarbonyls in neat conditions under MW irradiation promoted by DABCO as a solid organobase has been developed for the rapid construction of a novel class of densely functionalized picolinates. This interesting metal-solvent-free tactic allows a wide range of useful functionalities on the aryl rings and delivers good to excellent yields of the aforesaid aza-heterocycles within short time spans (20-40 min). A biologically promising imidazo[1,2-a]pyridine was successfully synthesized through our unique procedure.

A new synthetic strategy towards 2,4,5-trisubstituted 1H-imidazoles and highly substituted pyrrolo[1,2-c]imidazoles by use of α-azidochalcones via Michael addition-cyclization followed by Wittig reaction

Efficient and facile protocols for the preparation of highly functionalized 1H-imidazoles and 5H-pyrrolo[1,2-c]imidazoles are described. Heating a mixture of an α-azidochalcones and N,N,N′,N′-tetramethyl guanidine under neat conditions gave the corresponding 2,4,5-trisubstituted 1H-imidazole via Michael addition-cyclization in excellent yields. Subsequently, the prepared 1H-imidazoles undergo addition-Wittig reaction with acetylenic esters in presence of triphenylphosphine in dichloromethane to afford 5H-pyrrolo[1,2-c]imidazoles in high yields.

Crowders and Cosolvents-Major Contributors to the Cellular Milieu and Efficient Means to Counteract Environmental Stresses.

The free energy and conformational landscape of biomolecular systems as well as biochemical reactions depend not only on temperature and pressure, but also on the particular solution conditions. Such conditions include the effects of cosolvents (for example osmolytes) and macromolecular crowding, which are crucial components to understand the energetics and kinetics of biological processes in living system. Such conditions are also important for the understanding of many debilitating diseases, such as those where misfolding and amyloid formation of proteins are involved. Moreover, understanding their effects on biomolecular processes is prerequisite for designing industrially relevant enzymatic reactions, which seldom take place under neat conditions. Here, we review and discuss experimental and theoretical studies on the characterization of cosolvent and crowding induced effects in biologically relevant systems, approaching even the complexity of living organisms. In particular, we focus on cosolvent and crowding effects on the conformational equilibrium and folding kinetics of proteins and nucleic acids as well as on enzymatic reactions, including their effects on the temperature and pressure dependence of these processes. By presenting a few representative examples, we show how such effects are unveiled and described in thermodynamic and kinetic terms.

Sulfonamides and carbamates of 3-fluoro-4-morpholinoaniline (linezolid intermediate): synthesis, antimicrobial activity and molecular docking study

The precursor compound 3-fluoro-4-morpholinoaniline (7) is an important intermediate of the antibiotic drug linezolid and was synthesized initially by the substitution of morpholine (5) on 1,2-difluoro-4-nitrobenzene (4) under neat conditions, resulting in 4-(2-fluoro-4-nitrophenyl)morpholine (6) followed by its nitro group reduction with Fe/NH4Cl. A series of new sulfonamides (9a–e) and carbamates (11a–e) have been synthesized in good yields (75–89%) by the reaction of substituted aryl sulfonyl chlorides (8a–e) and substituted aryl/acyclic chloroformates (10a–e) with precursor compound 7, respectively, for biological interest. Structures of the title products were elucidated by spectroscopic data such as IR, NMR (1H and 13C NMR) and mass and elemental analyses. The antimicrobial potency of title products was examined by the screening of growth of zone of inhibition against four bacteria and four fungi, and minimum inhibitory concentration (MIC) was also determined. Most of the compounds showed good to potent antimicrobial activity, whereas the title products, 9d and 9e against bacterial strains, and 9a, 9b, 9d and 11a against fungi, exhibited promising activity in the MIC range of 6.25–25.0 µg/mL. The whole biological activity results revealed that the sulfonamide derivatives behaved as potent antifungal agents as compared to the carbamate derivatives. Molecular docking studies of the crystal structure of topoisomerase II gyrase A complexed with natural inhibitor, clorobiocin (1kzn), using the molecular operating environment (MOE) programme were performed in order to predict the affinity and orientation of the synthesized compounds at the active enzyme site. The test compounds showed good binding affinities and formed hydrogen bonds with a surrounding of amino acids at the active sight, whereas compounds 9d (−189.0 kcal/mol) and 11a (−280.3 kcal/mol) exhibited high binding affinities and good agreement with in vitro antimicrobial screening.

Non-isocyanate thermoplastic polyureas (NIPUreas) through a methyl carbamate metathesis polymerization

Non-isocyanate thermoplastic polyureas (NIPUreas) were synthesized using an original approach. Dimethyl dicarbamates (DC) were prepared as monomers, by the reaction of a diamine with an excess of dimethylcarbonate (DMC), in presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as catalyst. Then, self-polymerization of DC was performed through a methylcarbamate metathesis reaction, in presence of K2CO3 or TBD as catalysts. The reaction was conducted under neat conditions at 160 or 200°C. NIPUrea analogues were also synthesized by melt transurethane polycondensation between DC and corresponding diamine, in presence of K2CO3 or TBD as catalyst at 160°C. The thermal properties were dramatically dependent on the synthesis approach and operating conditions. The obtained NIPUreas displayed Tg values varying from −37 to 118°C, Tm values varying from 95 to 289°C, and thermal stabilities above 200°C. The metathesis reaction with TBD has been found not effective. Using K2CO3 as catalyst, metathesis seems to afford higher molecular weight comparing to transurethanization.

Bleaching Earths as Powerful Additives for Ru-Catalyzed Self-Metathesis of Non-Refined Methyl Oleate at Pilot Scale.

A practical and cost-effective ruthenium-catalyzed self-metathesis of non-refined methyl oleate (85 %) derived from very high oleic sunflower oils was demonstrated at pilot scale using a robust and kg-scale commercially available SIPr-M71 pre-catalyst. The simple addition of 1 wt % bleaching earths (Tonsil 110FF) to a thermally pretreated oil could efficiently prevent catalyst deactivation. Remarkably, without the need for filtration, the catalytic system was able to achieve a turnover number (TON) of more than 744 000 at a catalyst loading of only 1 ppm. At large scale (up to 200 kg), the equilibrium of the self-metathesis reaction was reached within 1 hour at 50 °C under neat conditions at a very low 5 ppm catalyst loading to produce the expected primary metathesis products (PMP), that is, 9-octadecene and dimethyl-9-octadecenoate, with a productive TON of 94900.

Selectively synthesis of cyclic di- and trithiocarbonates by N-heterocyclic carbene/LiCl(Br) catalyzed addition of carbon disulfide to epoxides

Carbon disulfide is an abundant, inexpensive and readily available material. One of the main challenges in the reaction of epoxides with CS2 is to control the chemoselectivity as a variety of compounds would be formed in the reaction. A simple and convenient method toward selectively synthesis of oxathiolane and trithiocarbonate from epoxides with CS2 catalyzed by NHC/LiCl(Br) under the neat conditions has been developed. This catalytic system exhibits excellent activity and selectivity in cycloaddition reactions of carbon disulfide to terminal epoxides.

Efficient Cu(OTf)2-catalyzed and microwave-assisted rapid synthesis of 3,4-fused chromenopyridinones under neat conditions

An efficient, solvent-free, environmentally benign, Cu(OTf)2-catalyzed and microwave-assisted fast synthesis of a fascinating class of a number of angularly fused chromenopyridinones having a carboxylate group at C-2 position on the pyridine ring via a one-pot [3+3] annulation reaction of several aminocoumarins/cyclic β-enaminones with different kinds of γ-aryl/styryl/heteroaryl-substituted-β,γ-unsaturated α-ketoesters as Michael acceptors under open atmosphere. This eco-friendly method delivers good to excellent yields of pyridine-fused-heterocycles within (15–40min) without using any traditional oxidants and allows several important functionalities. Furthermore, by this method, stereoselective synthesis of trans-7,8-diaryl-8.9-dihydrochromeno[4,3-b]cyclopenta[e]pyridine-6,10-diones were obtained in an excellent diastereoselective manner (dr≤99:1).

Supported and Unsupported Chiral Squaramides as Organocatalysts for Stereoselective Michael Additions: Synthesis of Enantiopure Chromenes and Spirochromanes.

Novel supported chiral bifunctional squaramides have been easily prepared starting from diamines derived from natural amino acids and commercially available aminoalkyl polystyrene resins. These squaramides behave as excellent stereoselective recoverable organocatalysts in different Michael additions, in neat conditions at room temperature. The reaction on 2-(2-nitrovinyl) phenol as electrophile lead, in excellent yields and enantioselectivities, to intermediates that can be easily transformed into 4H-chromenes, and spirochromanones.

Ligand-Accelerated Gold-Catalyzed Addition of in Situ Generated Hydrazoic Acid to Alkynes under Neat Conditions.

The direct addition of in situ generated hydrazoic acid to alkynes is realized without solvent by using a gold catalyst derived from a recently designed remotely functionalized biaryl-2-ylphosphine ligand (i.e., WangPhos). With terminal alkynes, the additions are mostly realized with 0.1 mol% catalyst loadings and at 40 °C. With more challenging internal alkynes devoid of direct EWG substitution, the one-step transformation is realized for the first time with generally high efficiency at ambient temperature.

Diethyldisulfoammonium chlorometallates as heterogeneous Brønsted–Lewis acidic catalysts for one‐pot synthesis of 14‐aryl‐7‐(N‐phenyl)‐14H‐dibenzo[a,j]acridines

A new series of Brønsted–Lewis acidic diethyldisulfoammonium chlorometallates, [DEDSA][FeCl4] and [DEDSA]2[Zn2Cl6], were synthesized as solid materials from the reaction of [(Et)2N(SO3H)2][Cl] ionic liquid with transition metal chlorides (FeCl3 and ZnCl2) at 80 °C in neat condition for 2 h. The chlorometallates were fully characterized using various spectroscopic and analytical techniques such as Fourier transform infrared, UV–visible and Raman spectroscopies, powder X‐ray diffraction, scanning electron microscopy, energy‐dispersive X‐ray and thermogravimetric analyses, Hammett acidity and elemental analyses. Their catalytic activity was studied as reusable heterogeneous catalysts for the three‐component synthesis of novel 14‐aryl‐7‐(N‐phenyl)‐14H‐dibenzo[a,j]acridines under solvent‐free conditions at 100 °C.