One-Pot Synthesis

An efficient one-pot method for synthesis of an array of 3,4-dihydroquinazolin-4-ones from anthranilicacid, triethyl orthoformate, and anilines using oxalic acid as a catalyst was described. The present protocol offers improvements for the synthesis of 3,4-dihydroquinazolin-4-ones with regard to short reaction time, high yields of products, and simplicity in operation.

A one pot, three-component condensation of benzoin/benzyl, an aldehyde, and ammonium acetate using diethyl bromophosphate as a mild oxidant is achieved to form trisubstituted imidazole compounds. Under ultrasound irradiation, a smooth condensation occurs to get the 2, 4, 5-triaryl-1H-imidazole compounds in good to excellent yields. The study explores the scope and limitation of diethyl bromophosphate as an oxidant and suggests advantages, viz., simplicity of operation, reduction in time, and an increase in product yields.

Chitosan is functionalized with poly(ethylene glycol) methyl ether (mPEG) at the amino and hydroxyl groups via a single step reaction in a homogeneous aqueous system. A chitosan aqueous solution obtained from the mixture of chitosan and hydroxybenzotriazole (HOBt) in water is a key factor in providing mild conditions to conjugate mPEG by using a carbodiimide conjugating agent. The reaction at ambient temperature for 24 h gives chitosan-g-mPEG with water solubility with mPEG content as high as 42%. This work demonstrates that a water-soluble chitosan-HOBt complex is an effective system for the preparation of chitosan derivatives via the aqueous system without the use of acids or organic solvents. #

Introduction
Sulfonamides have many biological activities, i.e. bacteriostatic, diuretic, anti-diabetic or anti-inflammatory. The discovery of an anti-cancer sulfonamide E7010 showed a new potential activity. Molecules containing 1,2,3-triazole group have strong activities too i.e. bactericidal, fungicidal, anti-inflammatory, anti-viral
and anti-neoplastic.

Aim of the study
Aim of the research was to find an effective one-pot, click-chemistry reaction to synthesize quinoline-based compounds with both sulfonamide and triazole groups. Obtained derivatives were to be tested for anti-neoplastic activity.

Material and methods
15 various 4-propargylamino-3-quinolinesulfonamides and 4-amino-3-quinoline-N-propargylsulfonamides were obtained from 4-chloro-3-quinolinesulfonamide chloride. Tested on cancer cell colonies, some of them showed moderate activity. They were used in 5 variants of azide-alkyne 1,3-cycloaddition:
• catalyst-free, solvent: H2O,
• two-phase with phase transfer catalyst (TEBA-Br),
• copper-catalyzed azide-alkyne cycloaddition (CuAAC),
solvents: DMF/H2O or tert-butanol,
• two-step: organic azide sythesis before CuAAC.
The reactions were made with 3 different halides: benzyl, allyl and 3-methyl-2-buten halide. Product structures were determined by 1H NMR and MS.

Results
13 derivatives of 4-amine-(N-4-methyl-1,2,3-triazol-4-yl)-3-quinolinesulfonamides and 4-amine-3-quinoline-N-(4-methyl-1,2,3-triazol-4-yl)sulfonamides were obtained. Benzyl halides yielded 80-90%, 3-methyl-2-buten halides: 70-80%, allyl halides: 40-50%.
Catalyst-free reaction did not occur, due to lack of substrate solubility. Thus it can be applied only for liquids creating water emulsions. Two-phase reaction caused difficulties in product purifying from TEBA-Br remains. Two-step reaction had good yields, but required organic azide synthesis before actual cycloaddition. One-pot CuAAC had good yields and simple ways of product separation: filtration or extraction.

Conclusion
The two last mentioned  methods seem to be most effective and variable in applications. The one-pot CuAAC may be best for chemical and pharmaceutical industry, due to its simplicity and short reaction time (24 to 48h).

Some new trifluoromethyl coumarin thiosemicarbazones 3a-3m were synthesized by condensation
reaction of thiosemicarbazides and 3-trifluoroacetyl coumarins which was from recyclization
of ethyl 2-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylates under microwave assisted
and solvent-free conditions. The structure of the synthesized compounds were characterized by IR, 1
H
NMR, 13C NMR, HRMS and X-ray, and their antifungal activity was evaluated. Most of them exhibited
potent antifungal activity by comparison with the standard drugs.

Abstract:  A novel Cu/Fe3O4 nanocomposite supported on carboxylate-rich carbon (Cu/Fe3O4@CRC) was successfully synthesized and characterized. The prepared composite was applied as an adsorbent and photo-Fenton-like catalyst for removal of methylene blue (MB). The results indicate that Cu/Fe3O4@CRC exhibited the highest adsorption and catalytic activities toward MB at the Fe/Cu molar ratio of 1:1 and 1:0.5, respectively. The adsorption process was thermodynamically spontaneous, endothermic, and followed well pseudo-first-order kinetic and the Freundlich isotherm models. The maximum adsorption capacity was found to be 240.27 mg g-1 at pH 7, the contact time of 40 min and temperature of 25 oC. The photo-Fenton degradation efficiency achieved 97.5% under visible light irradiation for 40 min at optimal conditions of MB concentration of 40 mg L-1, catalyst dosage of 0.2 g L-1, pH 6.0, and H2O2 concentration of 4 mmol L-1. Besides, Cu/Fe3O4@CRC displayed a high removal efficiency and stability after five reaction cycles.  Journal Pre-proof

The present article describes a facile one-pot synthesis of a series of eight pyrazolo[3,4-d]pyrimidines 4a–h which were evaluated for their in-vitro antibacterial activity against Mycobacterium tuberculosis H37Rv using the Alamar-Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC) in mg/mL. The compounds 4b, 4c, 4d, and 4g exhibited the best results (1.2 μg/mL) when compared with first-line drugs such as isoniazid (INH) and rifampicin (RIP). Therefore, this class of compounds could be a good starting point to develop new lead compounds in the treatment of multidrug-resistant tuberculosis.

Sulfonamides are a huge group of compounds with various biological activities (antihistamine, antibacterial, antiviral and antineoplastic). The discovery of a new sulfonamide marked as E-7010 in 1992, caused increased interest in this chemical group and led to synthesis of many interesting antineoplastic compounds. Some of them are in advanced stage of clinical trials.

In our research over a dozen 4-propargylamino-3-quinolinesulfonamides [2] and 4-amino-3-quinoline-N-propargylsulfonamides [3] were synthesized lately from 4-chloro-3-quinolinesulfonamide chloride.

Sulfonamides [2] and [3] were tested on neoplastic cells, but their activity is relatively low. That is why a one-pot azide-acetylene addition reaction was performed on selected sulfonamides from groups [2] and [3]. The reaction was made in DMF-water solution, in room temperature for 24 hours, with copper(II) ions and ascorbic acid as catalysts. Obtained products were 1,2,3-triazole-substituted compounds, which yielded with 77-90%.

An efficient Ho3+ doped CoFe2O4 nanoparticles catalyzed one-pot synthesis of 2,4,5-triaryl-1H-imidazoles has been
developed via three-component condensation of benzil or benzoin, aromatic aldehydes, and ammonium acetate in
ethanol. The catalyst can be easily separable using magnet and reused with almost the same catalytic activity. The
proposed method is advantageous due to its little catalyst loading, short reaction time, catalyst reusability, and
excellent yields.

An efficient one-pot method for synthesis of an array of 3,4-dihydroquinazolin-4-ones from anthranilicacid, triethyl orthoformate, and anilines using oxalic acid as a catalyst was described. The present protocol offers improvements for the synthesis of 3,4-dihydroquinazolin-4-ones with regard to short reaction time, high yields of products, and simplicity in operation.

A simple and efficient synthesis of 4-aryl-4,5-dihydro-1H-indeno[1,2-b]pyridine derivatives has been achieved via a four-component cyclocondensation of 1,3-indanedione, aromatic aldehydes, b-ketoesters and ammonium acetate in one-pot in the absence of catalyst and solvent at room temperature on grinding. The present approach offers several advantages such as shorter reaction times, higher yields, low cost, simple work-up and easy purification.

A series of 2-amino-4-(nitroalkyl)-4H-chromene-3-carbonitriles were synthesized by an efficient multicomponent reaction in aqueous media using DBU as a catalyst at room temperature. Mild condition, environment friendly procedure and excellent yields are the main advantages of this procedure. The cytotoxic activity of target compounds were evaluated against three cancer cell lines MDA-MB-231, MCF-7 and T47D in comparison with etoposide as reference drug. Generally, all compounds showed good cell growth inhibitory activity with IC 50 values less than 30 μg/mL. Their activities were comparable or more potent than standard drug etoposide. The 6-bromo-derivatives 7e and 7f showed promising cytotoxic activity with IC 50 values in the range of 3.46-18.76 μg/mL, being more potent than etoposide against all tested cell lines.

Due to wide range of biological actions of sulfonamides, quinoline derivatives and 1,2,3-triazoles, as well as presence of this structures in substances bearing anticancer, antibacterial, antitubercular or beta-lactamase inhibiting activities, an effort was made to find an effective, one-pot method for synthesis of derivatives containing those three moieties.

Five "click chemistry" synthesis methods were evaluated:
-single-step CuAAC in DMFaq (A1) and tert-butanol/water (A2),
-single-step PTC method (B),
-two-step method using organic azide (C),
-single-step catalyst free (D).
The substrates were several 4-amino-3-quinolinesulfonamide analogs containing a propargyl group and four different halide types: benzyl bromide and chloride, allyl bromide and 1-bromo-3-methyl-2-buten.

13 new, not published in literature compounds were obtained. They were derivatives of: 4-amino-(N-methyl-1,2,3-triazolyl)-3-quinolinesulfonamides, 4-amino-3-quinoline-N-(4-methyl-1,2,3-triazolyl)sulfonamides and
4-chloro-3-quinoline-N-(methyl-1,2,3-triazolyl)sulfonamides. Yields were between 31 and 99%. Benzyl halide substrates yielded 65-99%, 1-bromo-3-methyl-2-butenu yielded 83-97%, and allyl bromide yielded 31-58%. There was no clear dependence of reaction yields on activity of halide type which was used as substrate.

It was concluded, that best methods for such syntheses are A1, A2, B and C. In most cases the only product was 1,4-disubstituted triazole. Method D has limited significance. For several obtained products a phenomenon similar to polymorphism may occur.

This work involves synthesis of thiazolidinone derivatives by condensation of various amines with different isothiocyanate with microwave assisted multicomponent reactions with microwaves (140watts) in a scientific microwave oven . The protocol is designed, carried out and successful completion of the reaction is confirmed by TLC. Library of such thiazolidinone derivatives has been generated and the structures were subjected to PASS for finding their probabilities of being active biologically. QSAR study of the library was done to find out most active molecules.3-Phenyl-5phenylamino-thiazolidin-4-one (Ia-1) where R = -C 6 H 5 R 1 = C 6 H 5 NH-is found most active compound as Antidiabetic

An unexpected one-pot tandem procedure of 2-bromo-4,5-diazafluoren-9-one starting from phenanthroline with a yield of up to 50% has been described. The conversion mechanism involves three consecutive oxidation, bromination, and rearrangement reactions. A series of its hammer-shaped donoreacceptor organic semiconductors with solvent-dependent fluorescence have also been constructed via Ullman and/or FriedeleCrafts reaction. Diazafluorenes (DAFs) and derivatives are regarded as promising building blocks or candidates for donoreacceptor organic semiconductors.

The regioselective C-3-O-acylation and O-methylation of a range of 4,6-O-benzylidene-beta-D-gluco- and galactopyranosides has been studied. Regioselectivity is achieved by forming the copper chelate of the 2,3-diol using either sodium hydride and copper(II) chloride, or copper(II) acetylacetanoate, or copper(II) acetate, prior to introduction of the acylating or methylating agent.

The efficient multicomponent synthesis of thiazolidinones from the reaction of arenealdehydes, mercaptoacetic acid and 2-picolilamine or 2-aminopyridine under ultrasound irradiation are reported. The reaction with 2-aminopyridine needs a Lewis acid catalysis to afford the corresponding 2-aryl-3-(pyridin-2-yl)-1,3-thiazolidin-4-ones. All novel compounds were identified and characterized by 1 H and 13 C NMR spectra. Applying the sonochemical methodology, two series of heterocyclic thiazolidinones were synthesized in good yields after short reaction times. j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / u l t s o n 2 J = 15.2); 3.88 (dd, 1H, H5a, 2 J = 15.6, 4 J = 1.9); 3.85 (d, 1H, CH 2 b, 2 J = 15.2); 3.79 (d, 1H, H5b, 2 J = 15.6). 13 C NMR d (100 MHz, ppm, 1 H NMR d (400 MHz, ppm, J H-H = Hz): 8.51 (d, 1H, py, 3 J = 3.9); 7.67 (td, 1H, py, 3 J = 7.8, 4 J = 2.0); 7.29 (dd, 1H, py, 3 J = 8.2, 4 J = 1.5); 7.21 (m, 2H, py and aryl); 7.11 (dd, 1H, aryl 3 J = .7.9, 4 J = 1.6); 6.93 (td, 1H, aryl, 3 J = 7.4, 4 J = 1.1); 6.86 (d, 1H, aryl, 3

A new unsymmetrical urea (N,N-dimethylisoindoline-2-carboxamide, DMIA), which is a potential candidate for urea herbicides, has been obtained in an efficient, one-pot reaction between 1,2-bis(bromomethyl)benzene and 1,1,3,3-tetramethylguanidine. The structure of the title compound has been studied by X-ray diffraction, ESI-MS, EI-MS, FT-IR and multinuclear NMR spectroscopy. The title compound crystallises in the centrosymmetric P2 1 /c space group of monoclinic system with a = 10.686(2)Å, b = 9.5519(19)Å, c = 11.179(2)Å, b = 117.36(1) o and Z = 4. X-ray single crystal analysis of DMIA shows the non-planar conformation of this molecule. Both nitrogen atoms exhibit distorted tetrahedral geometry. Between the molecules in the crystal there are no direction-specific interactions like hydrogen bonds. Arrangement of DMIA molecules is determined by the van der Waals interactions.

Dicationic room temperature ionic liquids (RTILs) based on 1-methylimidazolium salts with varying their
linkage chain between the cations were synthesized, characterized, and evaluated their catalytic activity
for the synthesis of 1,5-benzodiazepine derivatives under solvent free mild reaction condition. On screening,
all new synthesized imidazolium based dicationic RTILs showed efficient yields and selectivity of
respective benzodiazepine. Especially, 5 wt% of tetraethylene glycol-bis (3-methylimidazolium) diacetate
([tetraEG(mim)2][OAc]2) was found to be the best dicationic RTIL as catalyst for this reaction. All these
reactions were preceded very well under relatively mild reaction condition without addition of any
co-catalyst and solvent. The present RTILs catalytic system compared with several homogeneous,
heterogeneous catalysts. Moreover, effects of different solvent system on benzodiazepine reactions with
these RTILs were also determined.

A simple, straightforward, and highly efficient diastereoselective multicomponent one-pot synthesis of a series of pharmaceutically interesting functionalized piperidine derivatives has been developed based on a low-cost and environmentally benign Bi(NO 3) 3 Á5H 2 O catalyst via tandem reactions of 1,3-dicarbonyl compounds, aromatic aldehydes, and various amines in ethanol at room temperature. High atom-economy, good yields, eco-friendliness, and mild reaction conditions are some of the important features of this protocol.

— Results of comparative study for 3,3´-[(4-X-phenyl)methanediyl]bis(1H-indoles) synthesis starting from 4-X-benzaldehyde (X = H, OCH 3 , N(CH 3) 2 , NO 2 , OH) and 1H-indole in dichloromethane solution at room temperature and catalyzed by cerium trichloride heptahydrate or by new resin supported Ce(III) catalyst are described. It was found that Ce(III) cations supported on weakly acidic macroporous low-cost industrial resin have at least the same or better catalytic activity as CeCl 3 .7H 2 O (or other mentioned catalytic systems) advantageously its easy separation for a recycling.

The use of ionic liquids in catalysis is attracting ever more attention in chemical engineering. In line with this research we have studied Supported Ionic Liquid Catalysts (SILCAs) which consist of immobilized catalytic species, e.g. transition metal particles residing in an ionic liquid layer immobilized on a solid support. We found out that dissolution of Lewis or Brønsted acids into the ionic liquid layer of SILCA has major effects to the activity as well as the product distribution of the catalyst in citral transformation reactions. In fact, one-pot synthesis of menthols from citral was accomplished. The effects of different amounts of added Lewis and/or Brønsted acids to SILCA (one of them or both) were studied in this work.

A convenient one-pot four-component synthesis of tetrasubstituted pyrroles was carried out through the reaction of butane-2,3-dione with a-aminophosphorous ylides, obtained in situ from the 1 : 1 : 1 addition reaction between triphenylphosphine, dialkyl acetylenedicarboxylate, and ammonium acetate.

A novel organic-inorganic hybrid nanocatalyst, Ag nanoparticles supported poly propyl]aniline (Ag@PTMSPA), was prepared by a simple one-step method. X-ray diffraction analysis, field emission transmission electron microscopy and X-ray photo electron spectroscopy reveal the coexistence of Ag nanoparticles (average size ∼ 10 nm) and PTMSPA in Ag@PTMSPA. N 2 adsorption-desorption experiments provide the textural properties of the catalyst, such as surface area (86.6 m 2 /g), pore volume (1.3 × 10 − 1 cm 3 /g) and pore size (4.2 nm). UV-visible spectroscopy was used to follow the kinetics of reduction of 4-nitrophenol (4-NP) by sodium borohydride (NaBH 4 ) in the presence of Ag@PTMSPA catalyst.

We report a simple "one pot" single step method to synthesize sulfoalkyl ether -cyclodextrin (-CD) derivatives in aqueous solution, which avoids the limitations associated with commonly used organic synthesis of such derivatives including multi-step reactions, use of expensive, toxic, and often environmentally hazardous organic solvents and/or reagents. Using this method, we obtained sulfopropyl and sulfobutyl ethyl -CDs. We characterized these two derivatives and evaluated their ability to enhance solubility of fluconazole, a commonly used antifungal drug with poor water solubility. Experimental results indicate that these derivatives are structurally analogous to some of the commercially available -CD derivatives. More importantly, when they formed supramolecular inclusion complexes with fluconazole, they demonstrated similar, if not better, capacity to enhance fluconazole solubility compared with commercially available -CD derivatives, suggesting that the simple "one pot" single step synthesis may provide an effective alternative approach to produce large quantity of -CD derivatives as pharmaceutical biomaterials for medicinal applications.

Abstract A facile and practical route for the high-yielding synthesis of various thiourea derivatives of carbohydrates has been accomplished through the coupling of carbohydrate-based azides and amines under Staudinger condition (PPh3/CS2). Structures of all the developed compounds have been elucidated using various spectroscopic techniques, including NMR, IR, and MS. Weak interactions within compound 3a have also been discussed through the analysis of its single crystal X-ray data. Graphical Abstract

Abstract The new anion [Cr2(CO(NH2)2)2(C6H4O7)2]2 − has been isolated in the complex [Cr(CO(NH2)2)6]2[Cr2(CO(NH2)2)2(C6H4O7)2]3. The crystals of this complex were obtained by a one-pot synthetic method using 1:1 molar ratio of hexaureachromium(III) chloride and trisodium citrate in aqueous medium. It was characterized by elemental analysis, IR spectroscopy and single crystal X-ray diffraction analysis. The compound crystallizes in space group R‾3 of the trigonal system with three formula units in a cell of dimensions a = b = 24.7461(4) A, c = 13.7204(3) A and γ = 120°. The crystal structure comprises the columns consisting of [Cr(CO(NH2)2)6]3 + cations surrounded by a cylinder of complex anions, [Cr2(CO(NH2)2)2(C6H4O7)2]2 − which are packed in a honeycomb-like manner. This supramolecular architecture is formed and stabilized by inter- and intramolecular N H⋯O hydrogen bonds.

The starting material azo-benzyloxy acetophenone (2) has been synthesized in three steps; the direct diazotization of p-aminoacetophenone and its coupling reaction with m-cresol gave azo-acetophenone (1), which was benzylated with p-chlorobenzylchloride to give the starting material (2). The later compound was subjected to the one-pot three-component condensation reaction with substituted benzaldehydes and phenylhydrazine in the presence of sodium hydroxide to afford the target molecule azo-pyrazoline derivatives (3a-e) in high yields and short reaction times. The structures of the synthesized compounds were elucidated by using FT-IR, 1 H NMR, 13 C NMR and 13 C DEPT 135 spectra. Cyclization Benzylation Diazotization Azo-pyrazoline One-pot synthesis Azo-acetophenone

Metallo-b-lactamases (MBLs), produced by an increasing number of bacterial pathogens, facilitate the hydrolysis of many commonly used b-lactam antibiotics. There are no clinically useful antagonists against MBLs. Two sets of tetrahydropyrimidine-2-thione and pyrrole derivatives were synthesized and assayed for their inhibitory effects on the catalytic activity of the IMP-1 MBL from Pseudomonas aeruginosa and Klebsiella pneumoniae. Nine compounds tested (1a, 3b, 5c, 6b, 7a, 8a, 11c, 13a, and 16a) showed micromolar inhibition constants (K i values range from 20-80 lM). Compounds 1c, 2b, and 15a showed only weak inhibition. In silico docking was employed to investigate the binding mode of each enantiomer of the strongest inhibitor, 5c (K i = 19 ± 9 lM), as well as 7a (K i = 21 ± 10 lM), the strongest inhibitor of the pyrrole series, in the active site of IMP-1.

A series of 2-amino-4-(nitroalkyl)-4H-chromene-3-carbonitriles were synthesized by an efficient multicomponent reaction in aqueous media using DBU as a catalyst at room temperature. Mild condition, environment friendly procedure and excellent yields are the main advantages of this procedure. The cytotoxic activity of target compounds were evaluated against three cancer cell lines MDA-MB-231, MCF-7 and T47D in comparison with etoposide as reference drug. Generally, all compounds showed good cell growth inhibitory activity with IC(50) values less than 30 μg/mL. Their activities were comparable or more potent than standard drug etoposide. The 6-bromo- derivatives 7e and 7f showed promising cytotoxic activity with IC50 values in the range of 3.46-18.76 μg/mL, being more potent than etoposide against all tested cell lines.

A simple and efficient method is developed for the synthesis of 2-(benzothiazol-2-yl)-3-(substituted phenyl)acrylonitrile from 2-(benzothiazole-2-yl)-3-oxopentanedinitrile and aromatic aldehydes in the presence of a catalytic amount of piperdine into ethanol at reflux. Advantage of this procedure is relatively good yields (81-86%) with short reaction times (1.5-3 h), under moderate reaction conditions and simple workup procedure, plus easy preparation and handling of the catalyst.

This work involves synthesis of thiazolidinone derivatives by condensation of various amines with different isothiocyanate with microwave assisted multicomponent reactions with microwaves (140watts) in a scientific microwave oven . The protocol is designed, carried out and successful completion of the reaction is confirmed by TLC. Library of such thiazolidinone derivatives has been generated and the structures were subjected to PASS for finding their probabilities of being active biologically. QSAR study of the library was done to find out most active molecules.3-Phenyl-5phenylamino-thiazolidin-4-one (Ia-1) where R = -C 6 H 5 R 1 = C 6 H 5 NH-is found most active compound as Antidiabetic

A one pot, three-component condensation of benzoin/benzyl, an aldehyde, and ammonium acetate using diethyl bromophosphate as a mild oxidant is achieved to form trisubstituted imidazole compounds. Under ultrasound irradiation, a smooth condensation occurs to get the 2, 4, 5-triaryl-1H-imidazole compounds in good to excellent yields. The study explores the scope and limitation of diethyl bromophosphate as an oxidant and suggests advantages, viz., simplicity of operation, reduction in time, and an increase in product yields.

We prepared a brand-new, bowl-shaped molecular architecture in one step from the reaction of ninhydrin and phloroglucinol in acetic acid in excellent yield (95%) in a one-pot reaction and the bipolarofacial nature of this compound was confirmed by its X-ray structure.